KR20220111915A - Anti-aging composition comprising a tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient - Google Patents
Anti-aging composition comprising a tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient Download PDFInfo
- Publication number
- KR20220111915A KR20220111915A KR1020210015323A KR20210015323A KR20220111915A KR 20220111915 A KR20220111915 A KR 20220111915A KR 1020210015323 A KR1020210015323 A KR 1020210015323A KR 20210015323 A KR20210015323 A KR 20210015323A KR 20220111915 A KR20220111915 A KR 20220111915A
- Authority
- KR
- South Korea
- Prior art keywords
- aging
- derivative compound
- present
- acceptable salt
- tryptamine derivative
- Prior art date
Links
- -1 tryptamine derivative compound Chemical class 0.000 title claims abstract description 40
- 239000000203 mixture Substances 0.000 title claims abstract description 34
- 150000003839 salts Chemical class 0.000 title claims abstract description 25
- 230000003712 anti-aging effect Effects 0.000 title claims abstract description 24
- 239000004480 active ingredient Substances 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 239000002537 cosmetic Substances 0.000 claims description 12
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 11
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 8
- 230000036541 health Effects 0.000 claims description 8
- 235000013376 functional food Nutrition 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 230000003078 antioxidant effect Effects 0.000 abstract description 14
- 230000004900 autophagic degradation Effects 0.000 abstract description 14
- 230000036542 oxidative stress Effects 0.000 abstract description 13
- 230000032683 aging Effects 0.000 abstract description 12
- 201000010099 disease Diseases 0.000 abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 230000002886 autophagic effect Effects 0.000 abstract description 2
- 230000008482 dysregulation Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 235000002639 sodium chloride Nutrition 0.000 description 20
- 102000004169 proteins and genes Human genes 0.000 description 19
- 108090000623 proteins and genes Proteins 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 18
- 239000000243 solution Substances 0.000 description 15
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 230000003834 intracellular effect Effects 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 9
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 9
- 239000003963 antioxidant agent Substances 0.000 description 8
- 235000006708 antioxidants Nutrition 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 7
- 229930003268 Vitamin C Natural products 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- 235000019154 vitamin C Nutrition 0.000 description 7
- 239000011718 vitamin C Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 210000002950 fibroblast Anatomy 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- ZTOJFFHGPLIVKC-YAFCTCPESA-N (2e)-3-ethyl-2-[(z)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound S\1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C/1=N/N=C1/SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-YAFCTCPESA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 102000007456 Peroxiredoxin Human genes 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- 230000002500 effect on skin Effects 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 230000008810 intracellular oxidative stress Effects 0.000 description 4
- 108030002458 peroxiredoxin Proteins 0.000 description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108010053835 Catalase Proteins 0.000 description 3
- 102000016938 Catalase Human genes 0.000 description 3
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 102000008221 Superoxide Dismutase-1 Human genes 0.000 description 3
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 238000001378 electrochemiluminescence detection Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 210000003470 mitochondria Anatomy 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102000006587 Glutathione peroxidase Human genes 0.000 description 2
- 108700016172 Glutathione peroxidases Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000019197 Superoxide Dismutase Human genes 0.000 description 2
- 108010012715 Superoxide dismutase Proteins 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 102000002933 Thioredoxin Human genes 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000008004 cell lysis buffer Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 210000005061 intracellular organelle Anatomy 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 210000002824 peroxisome Anatomy 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000013616 tea Nutrition 0.000 description 2
- 108060008226 thioredoxin Proteins 0.000 description 2
- 229940094937 thioredoxin Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- UHBGYHOPZPPYTP-UHFFFAOYSA-N 1H-imidazole sulfuryl diazide Chemical compound S(=O)(=O)(N=[N+]=[N-])N=[N+]=[N-].N1C=NC=C1 UHBGYHOPZPPYTP-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 238000010269 ABTS assay Methods 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 102000003954 Autophagy-Related Proteins Human genes 0.000 description 1
- 108010082399 Autophagy-Related Proteins Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 101000929971 Dianthus caryophyllus Probable 1-aminocyclopropane-1-carboxylate oxidase Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000733249 Homo sapiens Tumor suppressor ARF Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000019305 Microtubule associated protein 1A Human genes 0.000 description 1
- 108050006673 Microtubule associated protein 1A Proteins 0.000 description 1
- 102000004866 Microtubule-associated protein 1B Human genes 0.000 description 1
- 108090001040 Microtubule-associated protein 1B Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical compound OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241001122767 Theaceae Species 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- ZTOJFFHGPLIVKC-CLFAGFIQSA-N abts Chemical compound S/1C2=CC(S(O)(=O)=O)=CC=C2N(CC)C\1=N\N=C1/SC2=CC(S(O)(=O)=O)=CC=C2N1CC ZTOJFFHGPLIVKC-CLFAGFIQSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 102000011558 antioxidant activity proteins Human genes 0.000 description 1
- 108040004350 antioxidant activity proteins Proteins 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008952 bacterial invasion Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000013040 bath agent Substances 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000032677 cell aging Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000010094 cellular senescence Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 238000012650 click reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- FOYKKGHVWRFIBD-UHFFFAOYSA-N gamma-tocopherol acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 FOYKKGHVWRFIBD-UHFFFAOYSA-N 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical class C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 235000014705 isoleucine Nutrition 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940101267 panthenol Drugs 0.000 description 1
- 239000011619 pantothenol Substances 0.000 description 1
- 235000020957 pantothenol Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229940071089 sarcosinate Drugs 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000008234 soft water Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940104261 taurate Drugs 0.000 description 1
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- 229940117960 vanillin Drugs 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/496—Triazoles or their condensed derivatives, e.g. benzotriazoles
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/302—Foods, ingredients or supplements having a functional effect on health having a modulating effect on age
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Dermatology (AREA)
- Food Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
본 발명은 신규한 트립타민 유도체 또는 이의 약제학적으로 허용되는 염을 유효성분으로 포함하는 항노화용 조성물, 항노화용 화장료 조성물 및 항노화용 건강기능식품에 관한 것이다. The present invention relates to an anti-aging composition comprising a novel tryptamine derivative or a pharmaceutically acceptable salt thereof as an active ingredient, a cosmetic composition for anti-aging, and a health functional food for anti-aging.
세포 내 활성산소(ROS)는 세포의 대사과정 또는 박테리아 침입에 반응하는 과정에서 다양한 효소 반응에 의해 미토콘드리아, 퍼옥시좀, 소포체 등에서 생성되며, 활성산소의 생성 및 상기 활성산소를 제거하는 항산화 방어 기작의 불균형으로 인해 산화 스트레스가 발생한다. Intracellular reactive oxygen species (ROS) is produced in mitochondria, peroxisomes, endoplasmic reticulum, etc. by various enzymatic reactions in the process of cellular metabolism or in response to bacterial invasion. Oxidative stress occurs due to an imbalance of
산화 스트레스는 노화의 주요 발생 요인이다. 과도한 산화 스트레스에 의해 세포 내 단백질 또는 DNA의 손상이 발생하며, 이러한 손상이 복원되지 않거나 산화 스트레스가 제거되지 않고 계속 축적되면 미토콘드리아, 소포체 또는 퍼옥시좀 등의 세포 내 소기관들의 기능 이상이 발생하여, 결국 세포 기능의 이상이 발생하여 노화 및 노화 관련 질환들이 발병한다.Oxidative stress is a major cause of aging. Intracellular protein or DNA damage occurs due to excessive oxidative stress, and if the damage is not repaired or the oxidative stress is not removed and continues to accumulate, dysfunction of intracellular organelles such as mitochondria, endoplasmic reticulum, or peroxisomes occurs. Eventually, abnormal cell function occurs, leading to aging and aging-related diseases.
인체 세포 내에는 활성산소를 감소시키는 여러 기작이 있는데, 그 중 대표적인 것이 Superoxide dismutase(SOD), catalase, glutathione peroxidase(GTPx), thioredoxin(TRX), peroxiredoxin(PRX) 또는 glutathione transferase(GST)와 같은 항산화 단백질 효소에 의한 반응에 따른 활성산소 제거 및 비타민 C, 비타민 E, 카로티노이드 혹은 Glutathione 등의 항산화물질에 의한 활성산소 제거이다. There are several mechanisms that reduce free radicals in human cells, among which the representative ones are antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GTPx), thioredoxin (TRX), peroxiredoxin (PRX) or glutathione transferase (GST). Removal of free radicals according to the reaction by protein enzymes and removal of active oxygen by antioxidants such as vitamin C, vitamin E, carotenoids or glutathione.
뿐만 아니라, 자가포식(autophagy)를 통한 세포 내 산화 스트레스를 조절하는 세포 내 조절 기작이 있는데, 자가포식은 이중막 구조로 둘러싸인 세포 내 물질들을 리소좀(Lysosome)으로 전달하여 분해시키는 기작으로서, 세포 내 단백질의 질적 수준을 조절하는 중요한 역할을 하고 있다. 또한 구조 변형된 단백질 덩어리, 손상된 세포 내 소기관, 세포에 침입한 외부 병원균들의 제거에도 작용하여 세포 내 항상성 유지에 관여한다. In addition, there is an intracellular regulatory mechanism that regulates intracellular oxidative stress through autophagy. Autophagy is a mechanism for decomposing intracellular substances surrounded by a double membrane structure by delivering it to lysosomes. It plays an important role in regulating the quality level of proteins. In addition, it is involved in the maintenance of intracellular homeostasis by acting in the removal of structurally altered protein mass, damaged intracellular organelles, and foreign pathogens that have invaded the cell.
최근 다양한 연구를 통해 노화가 진행될수록 또는 노화를 가속화시킬수록 세포 내 자가포식 활성이 급격히 감소된다는 결과가 보고되고 있다. 자가포식이 억제된 세포에는 노후된 미토콘드리아나 잘못 접힌 단백질이 과도하게 축적되어, 세포 내 자유 라디칼 및 산화 스트레스가 증가하여 결국에 세포사멸로 이어지고, 노화 및 노화로 인한 질병이 촉진되는 결과가 야기된다. 이러한 자가포식의 비조절성으로 인해 암, 노화, 당뇨, 비만, 심장질환, 건선 및 아토피와 같은 다양한 질병들이 야기될 수 있다는 사실이 밝혀졌다.Recently, through various studies, it has been reported that as aging progresses or accelerates aging, the intracellular autophagy activity is rapidly reduced. Autophagy-inhibited cells accumulate aged mitochondria or misfolded proteins excessively, resulting in increased intracellular free radicals and oxidative stress, eventually leading to apoptosis, and accelerated aging and diseases caused by aging. It has been found that the deregulation of autophagy can lead to various diseases such as cancer, aging, diabetes, obesity, heart disease, psoriasis, and atopy.
한편, 항산화 물질로 널리 알려진 비타민 C는 공기 중에 쉽게 산화되며, 열에 약하고, 물에 용해된 상태에서는 매우 불안정할 뿐만 아니라 세포 내로 쉽게 침투하지 않기 때문에, 용매의 pH를 산성으로 조절함으로써 세포 침투율을 개선할 수 있지만 인체 피부세포의 pH보다 낮기 때문에 피부를 통한 세포 침투율은 여전히 장애가 남아 있다. 따라서 비타민 C와 동등하거나 또는 그 이상의 항산화 활성을 지니면서, 동시에 세포 내 산화 스트레스에 의해 생성된 노화된 물질 및 기관을 분해하고 그 분해산물을 재활용하도록 하는 자가포식 활성을 촉진시키고, 산화 스트레스에 의한 다양한 노화 관련 질병을 치료 및 예방하는 소재의 개발이 요구된다. On the other hand, vitamin C, which is widely known as an antioxidant, is easily oxidized in the air, is weak to heat, and is very unstable when dissolved in water and does not easily penetrate into cells. However, since it is lower than the pH of human skin cells, the rate of cell penetration through the skin remains an obstacle. Therefore, while having antioxidant activity equal to or higher than that of vitamin C, at the same time, it promotes autophagy activity that decomposes aged substances and organs generated by intracellular oxidative stress and recycles the decomposition products, and The development of materials for treating and preventing various age-related diseases is required.
본 발명은 세포 노화의 직접적 원인이 되는 산화 스트레스를 완화시키기 위한 항노화 및 자가포식 활성 효과를 동시에 갖는 트립타민 유도체 화합물 또는 이의 약제학적으로 허용가능한 염을 포함하는 항노화용 조성물을 제공하는 것을 목적으로 한다.The present invention aims to provide an anti-aging composition comprising a tryptamine derivative compound or a pharmaceutically acceptable salt thereof having both anti-aging and autophagic activity for alleviating oxidative stress, which is a direct cause of cellular aging. do.
본 발명은 항노화용 화장료 조성물을 제공하는 것으로, 구체적으로 세포 내 자가포식 활성화와 항산화 활성을 증가시킴으로써 노화에 의한 산화 스트레스를 감소시키는 작용을 하는 하기 화학식 1 로 표시되는 트립타민 유도체 화합물 또는 이의 약제학적으로 허용되는 염을 유효성분으로 포함하는 항노화용 조성물을 제공한다.The present invention provides a cosmetic composition for anti-aging, specifically, a tryptamine derivative compound represented by the following formula (1), which reduces oxidative stress due to aging by increasing intracellular autophagy activation and antioxidant activity, or a pharmaceutical thereof It provides an anti-aging composition comprising an acceptable salt as an active ingredient.
[화학식 1][Formula 1]
상기 화학식 1에서,In Formula 1,
R1 은 수소, 할로겐, C1-C10알킬, 또는 C1-C10알콕시이고;R 1 is hydrogen, halogen, C1-C10 alkyl, or C1-C10 alkoxy;
L은 NH 또는 O이고;L is NH or O;
R2는 C6-C20아릴, C3-C20헤테로아릴 또는 5원 내지 7원의 헤테로시클로알킬이고, 상기 R2의 아릴 및 헤테로아릴은 독립적으로 할로겐, C1-C10알킬, C1-C10알콕시, C1-C10알킬싸이오 또는 나이트릴로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있다.R 2 is C6-C20 aryl, C3-C20 heteroaryl, or 5 to 7 membered heterocycloalkyl, and aryl and heteroaryl of R 2 are independently halogen, C1-C10 alkyl, C1-C10 alkoxy, C1- It may be further substituted with one or more selected from the group consisting of C10 alkylthio or nitrile.
본 발명의 일 구현예에 있어서, 상기 화학식 1에서 R1은 수소 또는 C1-C4알콕시이고; L은 NH이고; R2는 C6-C20아릴이고; 상기 R2의 아릴은 C1-C10알킬로 더 치환된 것일 수 있다.In one embodiment of the present invention, in
본 발명의 일 구현예에 있어서, 상기 화학식 1로 표시되는 트립타민 유도체 화합물은 하기 화합물로부터 선택될 수 있다.In one embodiment of the present invention, the tryptamine derivative compound represented by Formula 1 may be selected from the following compounds.
본 발명의 일 구현예에 있어서, 상기 화학식 1로 표시되는 트립타민 유도체 화합물은 하기 화합물로부터 선택될 수 있다.In one embodiment of the present invention, the tryptamine derivative compound represented by Formula 1 may be selected from the following compounds.
또한 본 발명은 상술한 트립타민 유도체 화합물 또는 이의 약제학적으로 허용되는 염을 유효성분으로 포함하는 항노화용 화장료 조성물을 제공한다.The present invention also provides a cosmetic composition for anti-aging comprising the above-described tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient.
또한 본 발명은 상술한 트립타민 유도체 화합물 또는 이의 약제학적으로 허용되는 염을 유효성분으로 포함하는 항노화용 건강기능식품을 제공한다.In addition, the present invention provides a health functional food for anti-aging comprising the above-described tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 신규한 트립타민 유도체 화합물 또는 이의 약제학적으로 허용가능한 염을 포함하는 항노화용 조성물은 자가포식 관련 단백질의 발현을 증가시켜 자가포식을 활성화하여 산화 스트레스로부터 세포 보호 효과가 뛰어나며, 산화 스트레스로 인한 각종 질환의 예방 및 개선 효과를 제공할 수 있다.The anti-aging composition comprising the novel tryptamine derivative compound of the present invention or a pharmaceutically acceptable salt thereof increases the expression of autophagy-related proteins to activate autophagy, thereby having an excellent cell protection effect from oxidative stress. It can provide the effect of preventing and improving various diseases caused by.
또한 본 발명의 신규한 트립타민 유도체 화합물 또는 이의 약제학적으로 허용가능한 염을 포함하는 항노화용 조성물은 높은 항산화능과 함께 항산화 단백질들의 발현을 증가시켜 세포 내 산화 스트레스를 제거함으로써, 산화 스트레스로 인한 세포 손상 개선에 매우 효과적이다. In addition, the anti-aging composition comprising the novel tryptamine derivative compound or a pharmaceutically acceptable salt thereof of the present invention increases the expression of antioxidant proteins with high antioxidant activity to remove intracellular oxidative stress, thereby reducing the oxidative stress in cells caused by oxidative stress. It is very effective in improving damage.
도 1은 본 발명의 화합물 A-1 및 A-2의 처리에 의해 자가포식 활성화 단백질 발현을 분석한 결과이다.
도 2는 본 발명의 화합물 A-1 및 A-2의 항산화 활성능을 분석한 결과이다.
도 3은 본 발명의 화합물 A-1 및 A-2의 처리에 의해 항산화 활성 단백질 발현을 분석한 결과이다.
도 4는 본 발명의 화합물 A-1 및 A-2의 처리에 의해 노화관련 단백질 발현을 분석한 결과이다.1 is a result of analyzing the expression of autophagy activation protein by treatment with the compounds A-1 and A-2 of the present invention.
2 is a result of analyzing the antioxidant activity of the compounds A-1 and A-2 of the present invention.
3 is a result of analyzing the expression of antioxidant activity protein by treatment with the compounds A-1 and A-2 of the present invention.
4 is a result of analyzing the expression of aging-related proteins by treatment with the compounds A-1 and A-2 of the present invention.
이하, 본 발명에 대하여 보다 구체적으로 설명한다. 이 때 사용되는 기술 용어 및 과학 용어에 있어서 다른 정의가 없다면, 이 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 통상적으로 이해하고 있는 의미를 가지며, 하기의 설명에서 본 발명의 요지를 불필요하게 흐릴 수 있는 공지 기능 및 구성에 대한 설명은 생략한다.Hereinafter, the present invention will be described in more detail. If there is no other definition in the technical and scientific terms used at this time, it has the meaning commonly understood by those of ordinary skill in the art to which this invention belongs, and may unnecessarily obscure the subject matter of the present invention in the following description. Descriptions of possible known functions and configurations will be omitted.
본 발명에 기재된 용어 「알킬」은 탄소 및 수소 원자만으로 구성된 1가의 직쇄 또는 분쇄 포화 탄화수소 라디칼을 의미하는 것으로, 이러한 알킬 라디칼의 예는 메틸, 에틸, 프로필, 이소프로필, 부틸, 이소부틸, t-부틸, 펜틸, 헥실, 옥틸 등을 포함하지만 이에 한정되지는 않는다.As used herein, the term “alkyl” refers to a monovalent straight-chain or branched saturated hydrocarbon radical composed of only carbon and hydrogen atoms, and examples of such alkyl radicals include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t- butyl, pentyl, hexyl, octyl, and the like.
본 발명에 기재된 용어 「알콕시」는 -O-알킬 라디칼을 의미하는 것으로, 여기서 ‘알킬’은 상기 정의한 바와 같다. 이러한 알콕시 라디칼의 예는 메톡시, 에톡시, 이소프로폭시, 부톡시, 이소부톡시, t-부톡시 등을 포함하지만 이에 한정되지는 않는다. As used herein, the term “alkoxy” refers to an —O-alkyl radical, where “alkyl” is as defined above. Examples of such alkoxy radicals include, but are not limited to, methoxy, ethoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, and the like.
본 발명에 기재된 용어 「아릴」은 하나의 수소 제거에 의해서 방향족 탄화수소로부터 유도된 유기 라디칼로서, 각 고리에 적절하게는 4 내지 7개, 바람직하게는 5 또는 6개의 고리원자를 포함하는 단일 또는 융합고리계를 포함하며, 다수개의 아릴이 단일결합으로 연결되어 있는 형태까지 포함한다. 구체적인 예로 페닐, 나프틸, 비페닐, 안트릴, 인데닐(indenyl), 플루오레닐 등을 포함하지만, 이에 한정되지는 않는다. As used herein, the term "aryl" is an organic radical derived from an aromatic hydrocarbon by removal of one hydrogen, and is preferably a single or fused group containing 4 to 7, preferably 5 or 6 ring atoms in each ring. It includes a ring system, and includes a form in which a plurality of aryls are connected by a single bond. Specific examples include, but are not limited to, phenyl, naphthyl, biphenyl, anthryl, indenyl, fluorenyl, and the like.
본 발명에 기재된 용어「헤테로아릴」은 방향족 고리 골격 원자로서 N, O 및 S로부터 선택되는 1 내지 4개의 헤테로원자를 포함하고, 나머지 방향족 고리 골격 원자가 탄소인 아릴 그룹을 의미하는 것으로, 5 내지 6원 단환 헤테로아릴, 및 하나 이상의 벤젠환과 축합된 다환식 헤테로아릴이며, 부분적으로 포화될 수도 있다. 또한, 본 발명에서의 헤테로아릴은 하나 이상의 헤테로아릴이 단일결합으로 연결된 형태도 포함한다. 상기 헤테로아릴기의 예는 피롤, 퀴놀린, 이소퀴놀린, 피리딘, 피리미딘, 옥사졸, 티아졸, 티아디아졸, 트리아졸, 이미다졸, 벤조이미다졸, 이소옥사졸, 벤조이소옥사졸, 티오펜, 벤조티오펜, 퓨란, 벤조퓨란 등을 포함하지만, 이에 한정되지는 않는다. As used herein, the term "heteroaryl" refers to an aryl group containing 1 to 4 heteroatoms selected from N, O and S as aromatic ring skeleton atoms, and the remaining aromatic ring skeleton atoms are carbon, and 5 to 6 membered monocyclic heteroaryl, and polycyclic heteroaryl condensed with one or more benzene rings, which may be partially saturated. In addition, heteroaryl in the present invention includes a form in which one or more heteroaryl is connected by a single bond. Examples of the heteroaryl group include pyrrole, quinoline, isoquinoline, pyridine, pyrimidine, oxazole, thiazole, thiadiazole, triazole, imidazole, benzoimidazole, isoxazole, benzoisoxazole, thiophene, benzothiophene, furan, benzofuran, and the like.
본 발명에 기재된 용어 「헤테로사이클로알킬」은 N, O 및 S로부터 선택되는 하나 이상의 헤테로원자를 포함하는 5원 내지 7원의 고리로, 피롤리딘, 다이티올란, 모폴린, 이미다졸리딘, 테트라하이드로티오펜, 테트라하이드로퓨란 등을 포함하지만, 이에 한정되지는 않는다. As used herein, the term "heterocycloalkyl" is a 5- to 7-membered ring containing one or more heteroatoms selected from N, O and S, pyrrolidine, dithiolane, morpholine, imidazolidine, tetrahydrothiophene, tetrahydrofuran, and the like.
본 발명에 기재된 용어 「할로겐」은 불소, 염소, 브롬 또는 요오드 원자를 의미한다.As used herein, the term "halogen" means a fluorine, chlorine, bromine or iodine atom.
이하 본 발명에 따른 항노화용 조성물에 대하여 상세히 설명한다. Hereinafter, the composition for anti-aging according to the present invention will be described in detail.
본 발명은 하기 화학식 1 로 표시되는 트립타민 유도체 화합물 또는 이의 약제학적으로 허용되는 염을 유효성분으로 포함하는 항노화용 조성물을 제공한다.The present invention provides an anti-aging composition comprising a tryptamine derivative compound represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Formula 1]
상기 화학식 1에서,In Formula 1,
R1 은 수소, 할로겐, C1-C10알킬, 또는 C1-C10알콕시이고;R 1 is hydrogen, halogen, C1-C10 alkyl, or C1-C10 alkoxy;
L은 NH 또는 O이고;L is NH or O;
R2는 C6-C20아릴, C3-C20헤테로아릴 또는 5원 내지 7원의 헤테로시클로알킬이고, 상기 R2의 아릴 및 헤테로아릴은 독립적으로 할로겐, C1-C10알킬, C1-C10알콕시, C1-C10알킬싸이오 또는 나이트릴로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있다.R 2 is C6-C20 aryl, C3-C20 heteroaryl, or 5 to 7 membered heterocycloalkyl, and aryl and heteroaryl of R 2 are independently halogen, C1-C10 alkyl, C1-C10 alkoxy, C1- It may be further substituted with one or more selected from the group consisting of C10 alkylthio or nitrile.
바람직하게는 상기 화학식 1에서 R1은 수소 또는 C1-C10알콕시이고; L은 NH이고; R2는 C6-C20아릴이고; 상기 R2의 아릴은 할로겐, C1-C10알킬, C1-C10알콕시, C1-C10알킬싸이오 및 나이트릴로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있다. 보다 바람직하게는 R1은 수소 또는 C1-C4알콕시이고; L은 NH이고; R2는 C6-C20아릴이고; 상기 R2의 아릴은 C1-C10알킬로 더 치환된 것일 수 있다.Preferably, in
상기 화학식 1로 표시되는 트립타민 유도체 화합물 또는 이의 약제학적으로 허용되는 염을 포함하는 조성물은 자가포식을 유도하는 활성을 가지고 있어, 자가포식 활성화를 통해 세포 내 산화 스트레스를 제거하는 효과가 우수하다. The composition comprising the tryptamine derivative compound represented by Formula 1 or a pharmaceutically acceptable salt thereof has an activity to induce autophagy, and thus has an excellent effect of removing intracellular oxidative stress through autophagy activation.
본 발명의 일 구현예에 있어서, 상기 화학식 1로 표시되는 트립타민 유도체 화합물은 하기 화합물로부터 선택될 수 있다.
In one embodiment of the present invention, the tryptamine derivative compound represented by
본 발명에 따른 상기 트립타민 유도체 화합물들은, 이후 설명하는 바와 같이, 공지된 방법 및/또는 유기합성 분야의 기술에 근간한 다양한 방법들에 의해 제조될 수 있으며, 하기의 제조방법들은 일부 예시에 지나지 않으며, 그 이외의 방법들도 존재할 수 있음은 물론이다.The tryptamine derivative compounds according to the present invention may be prepared by various methods based on known methods and/or techniques in the field of organic synthesis, as will be described later, and the following preparation methods are only some examples. It goes without saying that other methods may exist.
구체적으로 예를 들면, 상기 트립타민 유도체 화합물들은 아자이드 화합물 및 알킬 화합물의 클릭 반응으로 합성될 수 있고, 반응 생성물은 재결정 또는 크로마토그래피를 이용하여 분리 정제할 수 있다.Specifically, for example, the tryptamine derivative compounds may be synthesized by a click reaction of an azide compound and an alkyl compound, and the reaction product may be separated and purified using recrystallization or chromatography.
본 발명에 따른 상기 화학식 1로 표시되는 트립타민 유도체 화합물들은 물 또는 기타 유기 용매와 함께 수화물 또는 용매화물을 형성할 수 있고, 이러한 수화물 또는 용매화물도 마찬가지로 본 발명의 범주 내에 포함된다. 염 및 용매화물에 있어서 추가적 이온 및 용매의 잔기는 무독성일 것이 요구된다. 본 발명의 화합물은 상이한 동질이상 형태로 존재할 수 있고, 본 발명은 상기의 모든 형태들을 포함할 수 있다.The tryptamine derivative compounds represented by
본 발명에서의 약제학적으로 허용 가능한 염은 당해 기술 분야에서 통상적인 방법에 의해 제조될 수 있는 것으로, 예를 들면 염산, 브롬산, 황산, 황산수소나트륨, 인산, 질산, 탄산 등과 같은 무기산과의 염, 개미산, 초산, 프로피온산, 옥살산, 석신산, 벤조산, 시트르산, 말레인산, 말론산, 타르타르산, 글루콘산, 락트산, 게스티스산, 푸마르산, 락토비온산, 살리실릭산, 또는 아세틸살리실릭산(아스피린)과 같은 유기산과의 염, 글리신, 알라닌, 바닐린, 이소루신, 세린, 시스테인, 시스틴, 아스파라진산, 글루타민, 리진, 아르기닌, 타이로신, 프롤린 등과 같은 아미노산과의 염, 메탄설폰산, 에탄설폰산, 벤젠설폰산, 톨루엔설폰산 등과 같은 설폰산과의 염, 나트륨, 칼륨 등의 알칼리금속과의 반응에 의한 금속염, 또는 암모늄 이온과의 염일 수 있다. The pharmaceutically acceptable salt in the present invention can be prepared by a method conventional in the art, for example, with an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, sodium hydrogen sulfate, phosphoric acid, nitric acid, carbonic acid, etc. salt, formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, citric acid, maleic acid, malonic acid, tartaric acid, gluconic acid, lactic acid, gestisic acid, fumaric acid, lactobionic acid, salicylic acid, or acetylsalicylic acid (aspirin) ), salts with organic acids such as glycine, alanine, vanillin, isoleucine, serine, cysteine, cystine, aspartic acid, glutamine, lysine, arginine, tyrosine, proline, salts with amino acids, methanesulfonic acid, ethanesulfonic acid , a salt with a sulfonic acid such as benzenesulfonic acid or toluenesulfonic acid, a metal salt by reaction with an alkali metal such as sodium or potassium, or a salt with an ammonium ion.
본 발명은 상기 트립타민 유도체 화합물 또는 이의 약제학적으로 허용되는 염을 유효성분으로 포함하는 항노화용 화장료 조성물을 제공한다.The present invention provides a cosmetic composition for anti-aging comprising the tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 있어서 항노화용 화장료 조성물은 기능성 화장품(cosmedical, cosmeceutical)에 제공될 수 있다. 본 발명의 목적상 상기 기능성 화장품은 피부 주름 개선에 도움을 주는 제품을 의미할 수 있다.In the present invention, the cosmetic composition for anti-aging may be provided in functional cosmetics (cosmedical, cosmeceutical). For the purpose of the present invention, the functional cosmetics may refer to products that help improve skin wrinkles.
본 발명에 있어서, 화장료 조성물은 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어 용액, 유탁액, 현탁액, 페이스트, 크림, 로션, 겔, 파우더, 스프레이, 계면활성제-함유 클린징, 오일, 비누, 액체 세정료, 입욕제, 파운데이션, 메이크업베이스, 에센스, 화장수, 폼, 팩, 유연수, 선 스크린 크림 또는 선오일 등으로 제형화 될 수 있으나 이에 제한되는 것은 아니다.In the present invention, the cosmetic composition may be prepared in any conventionally prepared formulation, for example, a solution, emulsion, suspension, paste, cream, lotion, gel, powder, spray, surfactant-containing cleansing, oil , soap, liquid detergent, bath agent, foundation, makeup base, essence, lotion, foam, pack, soft water, sunscreen cream or sun oil, etc., but is not limited thereto.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다. 본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 또는 트라칸트 등이 이용될 수 있다.When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylglycol oil, glycerol fatty esters, fatty acid esters of polyethylene glycol or sorbitan. When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystals Sex cellulose, aluminum metahydroxide, bentonite, or tracanth may be used.
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. can
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additional chlorofluorohydrocarbon, propane /may contain propellants such as butane or dimethyl ether.
본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is a surfactant-containing cleansing agent, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide as carrier components Ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative or ethoxylated glycerol fatty acid ester may be used.
본 발명에 따른 화장료 조성물은 통상적으로 사용되는 항산화제, 안정화제, 용해화제, 비타민, 안료, 향료 등과 같은 통상적인 보조제 및 담체를 더 포함할 수 있다. 예를 들어, 상기 화장료 조성물에는 글리세린, 부틸렌글라이콜, 폴리옥시에칠렌 경화피마자유, 토코페릴 아세테이트, 시트릭산, 판테놀, 스쿠알란, 소듐 시트레이트, 알란토인 등의 보조성분이 추가로 더 포함될 수 있다.The cosmetic composition according to the present invention may further include conventional adjuvants and carriers such as commonly used antioxidants, stabilizers, solubilizers, vitamins, pigments, fragrances, and the like. For example, the cosmetic composition may further include auxiliary components such as glycerin, butylene glycol, polyoxyethylene hydrogenated castor oil, tocopheryl acetate, citric acid, panthenol, squalane, sodium citrate, and allantoin.
또한 본 발명은 상기 트립타민 유도체 화합물 또는 이의 약제학적으로 허용되는 염을 유효성분으로 포함하는 항노화용 건강기능식품을 제공한다.In addition, the present invention provides a health functional food for anti-aging comprising the tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에서 건강기능식품은 건강보조의 목적으로 특정성분을 원료로 하거나 식품 원료에 들어있는 특정성분을 추출, 농축, 정제, 혼합 등의 방법으로 제조, 가공한 식품을 말하며, 상기 성분에 의해 생체방어, 생체리듬의 조절, 질병의 방지와 회복 등 생체조절기능을 생체에 대하여 충분히 발휘할 수 있도록 설계되고 가공된 식품을 말하는 것으로서, 상기 건강기능식품은 질병의 예방 및 질병의 회복 등과 관련된 기능을 수행할 수 있다. 본 발명의 목적상 상기 건강기능식품은 항산화 활성을 증진시키기 위한 것으로, 예를 들어 활성산소로 인해 발생하는 질환들을 예방 및 개선하기 위한 것일 수 있다.In the present invention, health functional food refers to food manufactured and processed by methods such as extraction, concentration, purification, mixing, etc. of specific ingredients as raw materials or in food raw materials for the purpose of health supplementation. It refers to food designed and processed to sufficiently exert biological control functions such as defense, regulation of biological rhythm, prevention and recovery of disease, etc., wherein the health functional food performs functions related to disease prevention and disease recovery can do. For the purpose of the present invention, the health functional food is to promote antioxidant activity, for example, it may be for preventing and improving diseases caused by free radicals.
상기 식품의 종류에는 특별한 제한이 없다. 본 발명에 따른 상기 트립타민 유도체 화합물 또는 이의 약제학적으로 허용되는 염을 유효성분으로 포함하는 조성물을 당업자의 선택에 따라 식품에 포함될 수 있는 적절한 기타 보조 성분과 공지의 첨가제를 혼합하여 식품으로 제조할 수 있다. 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림 류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있다.There is no particular limitation on the type of the food. The composition comprising the tryptamine derivative compound or a pharmaceutically acceptable salt thereof according to the present invention as an active ingredient may be prepared as food by mixing appropriate other auxiliary ingredients that may be included in food and known additives according to the selection of those skilled in the art. can Examples of foods that can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complex, etc.
이하, 실시예 및 실험예를 통해 본 발명을 상세히 설명한다. 단, 하기의 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail through Examples and Experimental Examples. However, the following examples and experimental examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following examples.
[제조예 1] 화합물 1의 제조[Preparation Example 1] Preparation of
트립타민(Tryptamine) (3 g, 18 mmol)을 20 mL 메탄올(MeOH)에 녹인 후 Cs2CO3 (9.15g, 28mmol)를 0 ℃에서 소분하여 녹였다. TEA (2.5 mL, 18 mmol)을 0 ℃에서 적가하고, 10분 후 이미다졸 술포닐 아자이드(Imidazole sulfonly azide)를 0 ℃에서 소분하여 넣어준 후 상온까지 온도를 올려주고, 24시간 동안 교반하였다. 에틸아세테이트(EA) : 헥산(Hex) = 1 : 4 (부피비)의 용매 조건으로 반응 경과를 TLC로 확인 후에 회전증발농축기(rotary evaporator)를 이용하여 용매를 제거한 후, crude에 H2O 100 mL를 부어주고 반응을 종결시켜 디클로로메탄(DCM) 100 mL을 이용하여 유기물을 추출하였다. 이 과정을 세 번 반복 후에 무수 MgSO4를 이용하여 수분을 제거하고, MgSO4를 감압필터하여 제거한 후 용매를 제거하였다. 이후 crude product를 에틸아세테이트(EA) : 헥산(Hex) = 1 : 4 (부피비)의 용매 조건으로 컬럼 크로마토그래피(column chromatography)를 이용하여 분리 정제 진행하여 노란색 액체 화합물 1 (3g, 수율 86%)을 수득하였다.After dissolving tryptamine (3 g, 18 mmol) in 20 mL methanol (MeOH), Cs 2 CO 3 (9.15 g, 28 mmol) was dissolved in small portions at 0 °C. TEA (2.5 mL, 18 mmol) was added dropwise at 0 °C, and after 10 minutes, imidazole sulfonyl azide was added in portions at 0 °C, the temperature was raised to room temperature, and the mixture was stirred for 24 hours. . Ethyl acetate (EA) : Hexane (Hex) = 1 : 4 (volume ratio), after confirming the reaction progress by TLC, the solvent was removed using a rotary evaporator, and the crude H 2 O 100 mL was poured and the reaction was terminated, and organic matter was extracted using 100 mL of dichloromethane (DCM). After repeating this process three times, water was removed using anhydrous MgSO 4 , MgSO 4 was removed by vacuum filter, and then the solvent was removed. Then, the crude product was separated and purified using column chromatography under solvent conditions of ethyl acetate (EA): hexane (Hex) = 1: 4 (volume ratio), and yellow liquid compound 1 (3 g, yield 86%) was obtained.
IR (KBr, cm-1) : 3413(NH), 2091(N3);IR (KBr, cm −1 ): 3413 (NH), 2091 (N 3 );
1H NMR (CDCl3, 400MHz): δ 3.05 (t, J = 7.6 Hz, 2H), 3.55 (t, J = 7.2 Hz, 2H), 7.04 (s, 1H), 7.12 (t, J = 8.8 Hz, 1H), 7.20 (t, J = 8.2 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.98 (s, 1H) 1 H NMR (CDCl 3 , 400 MHz): δ 3.05 (t, J = 7.6 Hz, 2H), 3.55 (t, J = 7.2 Hz, 2H), 7.04 (s, 1H), 7.12 (t, J = 8.8 Hz) , 1H), 7.20 (t, J = 8.2 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.98 (s, 1H)
[실시예 1] 화합물 A-1의 합성[Example 1] Synthesis of compound A-1
o-toluidine (0.2 g, 1.86 mmol)을 ACN (1 mL)에 녹인 후 Cs2CO3 (0.61 g, 1.86 mmol)와 KI (0.03 g, 0.19 mmol)를 넣어주고, 10분간 상온에서 교반 후, 프로파길 브로마이드(propargyl bromide) (0.21 mL, 2.38 mmol)을 넣어주었다. 온도를 올려 24시간 동안 reflux를 진행하고, 용매를 제거한 후에 바로 추가 정제 없이 다음 반응에 사용하였다. 혼합물을 (DMF : H2O : t-BuOH = 2 : 2 : 1, 2.5 mL) 용매에 녹이고, 화합물 1(130 mg, 0.69 mmol)을 넣어, 10분간 상온에서 교반 후 CuSO4·5H2O (34 mg, 0.01 mmol), (+)-sodium L-ascorbate (27 mg, 0.01 mmol)을 넣어준 후 상온에서 24시간 동안 교반하였다. NH4Cl(aq) (300 mL)를 이용하여 반응을 종결시키고, DCM으로 2회 유기층을 추출하였다. 무수 MgSO4를 이용하여 용액의 수분을 제거한 후, 감압필터를 이용하여 무수 MgSO4를 제거한 후에 용액을 감압 농축하였다. 컬럼 크로마토그래피(EA : DCM = 1 : 4, Rf = 0.6, 500 mL)를 이용하여 흰색 고체 A-1(80 mg, 수율 13%)를 얻었다.After dissolving o-toluidine (0.2 g, 1.86 mmol) in ACN (1 mL), Cs 2 CO 3 (0.61 g, 1.86 mmol) and KI (0.03 g, 0.19 mmol) were added, and after stirring at room temperature for 10 minutes, Propagyl bromide (propargyl bromide) (0.21 mL, 2.38 mmol) was added. The temperature was raised and reflux was performed for 24 hours, and immediately after the solvent was removed, it was used for the next reaction without further purification. The mixture (DMF: H 2 O: t-BuOH = 2: 2: 1, 2.5 mL) was dissolved in a solvent, compound 1 (130 mg, 0.69 mmol) was added, and after stirring at room temperature for 10 minutes, CuSO 4 5H 2 O (34 mg, 0.01 mmol) and (+)-sodium L-ascorbate (27 mg, 0.01 mmol) were added, followed by stirring at room temperature for 24 hours. The reaction was terminated using NH 4 Cl (aq) (300 mL), and the organic layer was extracted twice with DCM. After removing moisture from the solution using anhydrous MgSO 4 , the anhydrous MgSO 4 was removed using a reduced pressure filter, and then the solution was concentrated under reduced pressure. Column chromatography (EA: DCM = 1: 4, R f = 0.6, 500 mL) was used to obtain a white solid A-1 (80 mg, yield 13%).
1H-NMR (DMSO-d6, 400MHz) δ 2.09 (s, 3H), 3.22 (t, J = 7.6 Hz, 2H), 4.33 (d, J = 6.0 Hz, 2H), 4.58 (t, J = 7.6 Hz, 2H), 5.32 (t, J = 6.0 Hz, 1H), 6.50 ~ 6.54 (m, 2H), M 6.95 ~ 6.98 (m, 3H), 7.05 ~ 7.09 (m, 2H), 7.33 (d, J = 8.0, 1H), 7.50 (d, J = 8.0, 1H), 7.90 (s, 1H), 10.83 (bs, 1H) 1 H-NMR (DMSO-d 6 , 400 MHz) δ 2.09 (s, 3H), 3.22 (t, J = 7.6 Hz, 2H), 4.33 (d, J = 6.0 Hz, 2H), 4.58 (t, J = 7.6 Hz, 2H), 5.32 (t, J = 6.0 Hz, 1H), 6.50 to 6.54 (m, 2H), M 6.95 to 6.98 (m, 3H), 7.05 to 7.09 (m, 2H), 7.33 (d, J = 8.0, 1H), 7.50 (d, J = 8.0, 1H), 7.90 (s, 1H), 10.83 (bs, 1H)
13C NMR (DMSO-d6, 100MHz) δ 18.12, 26.55, 19.38, 50.43, 110.01, 110.55, 111.89, 116.52, 118.65, 118.87, 121.53, 122.41, 123.02, 123.62, 127.15, 127.38, 130.18, 136.61, 146.47, 146.49 13 C NMR (DMSO-d 6 , 100 MHz) δ 18.12, 26.55, 19.38, 50.43, 110.01, 110.55, 111.89, 116.52, 118.65, 118.87, 121.53, 122.41, 123.02, 123.62, 127.15, 127.38, 130.18, 136.47 146.49
[실시예 2] 화합물 A-2의 합성[Example 2] Synthesis of compound A-2
아닐린(Aniline) (0.2 g, 2.14 mmol)을 아세토니트릴(acetonitrile) (1 mL)에 녹인 후 Cs2CO3 (0.7 g, 2.14 mmol)와 KI (0.04 g, 0.21 mmol)를 넣어주고, 10분간 상온에서 교반 한 후 프로파길 브로마이드 (0.23 mL, 3.00 mmol)을 넣어주었다. 온도를 올려 reflux를 24시간 동안 진행하였고, 용매를 제거한 후에 바로 추가 정제 없이 다음 반응에 사용하였다. 혼합물을 (DMF : H2O : t-BuOH = 2 : 2 : 1, 2.5 mL) 용매에 녹인 후 화합물 1(130 mg, 0.77 mmol)을 넣어준다. 10분간 상온에서 교반 후에 CuSO4˙5H2O (38 mg, 0.15 mmol), (+)-sodium L-ascorbate (30 mg, 0.15 mmol)을 넣어준 후 상온에서 24시간 동안 교반하였다. NH4Cl(aq) 300 mL를 이용하여 반응을 종결시킨 후에 DCM으로 2회 유기층을 추출하였다. 무수 MgSO4를 이용하여 용액의 수분을 제거한 후, 감압필터를 이용하여 무수 MgSO4를 제거한 후에 용액을 감압 농축하였다. 컬럼 크로마토그래피 (EA : DCM = 1 : 6, Rf = 0.6, 400 mL)를 이용하여 연갈색 고체 (130 mg, 수율 19%)를 얻었다.After dissolving Aniline (0.2 g, 2.14 mmol) in acetonitrile (1 mL), Cs 2 CO 3 (0.7 g, 2.14 mmol) and KI (0.04 g, 0.21 mmol) were added, and 10 minutes After stirring at room temperature, propargyl bromide (0.23 mL, 3.00 mmol) was added thereto. The temperature was raised and reflux was performed for 24 hours, and immediately after the solvent was removed, it was used for the next reaction without further purification. The mixture (DMF: H 2 O: t-BuOH = 2: 2: 1, 2.5 mL) was dissolved in a solvent, and then Compound 1 (130 mg, 0.77 mmol) was added. After stirring at room temperature for 10 minutes, CuSO 4 ˙H 2 O (38 mg, 0.15 mmol) and (+)-sodium L-ascorbate (30 mg, 0.15 mmol) were added, followed by stirring at room temperature for 24 hours. After the reaction was terminated using 300 mL of NH 4 Cl (aq) , the organic layer was extracted twice with DCM. After removing moisture from the solution using anhydrous MgSO 4 , the anhydrous MgSO 4 was removed using a reduced pressure filter, and then the solution was concentrated under reduced pressure. Column chromatography (EA : DCM = 1 : 6, R f = 0.6, 400 mL) was used to obtain a light brown solid (130 mg, yield 19%).
1H NMR (DMSO-d6, 400MHz) δ 3.23 (t, J = 8.0 Hz, 2H) 4.24 (d, J = 6.0 Hz, 2H), 4.58 (t, J = 8.0 Hz, 2H), 5.98 (t, J = 6.0 Hz, 1H), 6.53 (t, J = 8.0 Hz, 1H), 6.60 (d, J = 8.0 Hz, 2H), 6.97 (t, J = 8.0 Hz, 1H), 7.04 ~ 7.08 (m, 4H), 7.33 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.94 (s, 1H), 10.83 (bs, 1H) 1 H NMR (DMSO-d 6 , 400 MHz) δ 3.23 (t, J = 8.0 Hz, 2H) 4.24 (d, J = 6.0 Hz, 2H), 4.58 (t, J = 8.0 Hz, 2H), 5.98 (t) , J = 6.0 Hz, 1H), 6.53 (t, J = 8.0 Hz, 1H), 6.60 (d, J = 8.0 Hz, 2H), 6.97 (t, J = 8.0 Hz, 1H), 7.04 to 7.08 (m) , 4H), 7.33 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.94 (s, 1H), 10.83 (bs, 1H)
13C NMR (DMSO-d6, 100MHz) δ 26.56, 39.15, 50.41, 110.53, 111.90, 112.80 (2C), 116.47, 118.64, 118.89, 121.54, 123.09, 123.63, 127.38, 129.30 (2C), 136.62, 146.07, 148.90 13 C NMR (DMSO-d 6 , 100 MHz) δ 26.56, 39.15, 50.41, 110.53, 111.90, 112.80 (2C), 116.47, 118.64, 118.89, 121.54, 123.09, 123.63, 127.38, 129.30 (2C), 136.62, 146.07,62 148.90
[실험예 1] 화합물 A-1 및 A-2에 의한 자가포식 활성 분석[Experimental Example 1] Autophagy activity analysis by compounds A-1 and A-2
본 발명의 트립타민 유도체 화합물 A-1 및 A-2의 처리에 의한 세포 내 자가포식 활성 증가를 분석하기 위해 LC3(light chain 3) 단백질에 대한 웨스턴 블랏을 수행하였다. In order to analyze the increase in intracellular autophagy activity by treatment with the tryptamine derivative compounds A-1 and A-2 of the present invention, Western blotting was performed on LC3 (light chain 3) protein.
사람섬유아세포인 HDF (Human dermal fibroblast)는 배양용 6-웰플레이트에 1 X 104 개의 세포 수로 일정하게 분주하여 DF-1 배지(Dermal Fibroblast Growth Medium, Zenbio)에서 24시간 동안 37℃, 5% CO2 조건으로 인큐베이터로 배양하였다. 화합물 A-1을 10 μM의 농도로 처리한 후, 일정 시간 동안 배양하고, 배양 종료 후 배지를 제거한 후 배양한 세포를 단백질 분해 억제제가 포함되어 있는 세포 용해 버퍼 (cell lysis buffer)을 이용하여 용해시켰다. 상기 용해된 용액을 원심분리기를 이용하여 전체 용액을 분획한 뒤, 단백질이 포함된 용액만을 추출하였다. 상기 추출된 단백질은 BCA (Bicinchoninic acid) 방법에 의해 정량화하였다. 20 ㎍의 단백질을 10% SDS-폴리아크릴아미드 겔 전기영동법으로 분리하고 니트로셀룰로오스 막에 옮겼다. 비특이적인 단백질 결합을 줄이기 위하여 5% 탈지유가 포함된 TBS-T (Tris-buffered saline/0.05% Tween-20) 용액으로 상온에서 1시간 동안 차단한 후, 1차 항체를 4 ℃ 조건에서 하룻밤(overnight) 동안 반응시킨 뒤 2차 항체를 1시간 동안 상온에서 반응시켰다. ECL prime kit(Amersham pharmacia)를 이용한 Enhanced chemiluminescence(ECL) 반응을 시켜, ChemiDoc 분석을 수행하였다.Human dermal fibroblasts (HDFs), which are human fibroblasts, were uniformly aliquoted at the number of 1 X 10 4 cells in a 6-well plate for culture and placed in DF-1 medium (Dermal Fibroblast Growth Medium, Zenbio) at 37°C, 5% for 24 hours. Incubated in an incubator under CO 2 conditions. After treatment with Compound A-1 at a concentration of 10 μM, incubated for a certain period of time, and after the culture was terminated, the cultured cells were lysed using a cell lysis buffer containing a proteolytic inhibitor. did it After fractionating the whole solution using a centrifuge for the dissolved solution, only the solution containing the protein was extracted. The extracted protein was quantified by BCA (Bicinchoninic acid) method. 20 μg of protein was separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. To reduce non-specific protein binding, after blocking with a TBS-T (Tris-buffered saline/0.05% Tween-20) solution containing 5% skim milk at room temperature for 1 hour, the primary antibody was incubated at 4 ° C overnight (overnight). ), and then the secondary antibody was reacted at room temperature for 1 hour. Enhanced chemiluminescence (ECL) reaction using ECL prime kit (Amersham pharmacia) was performed, and ChemiDoc analysis was performed.
그 결과를 도 1에 나타내었으며, 도 1에서 알 수 있는 바와 같이, 본 발명의 트립타민 유도체 화합물 A-1에 의해 LC3-Ⅱ(Microtubule-associated protein 1A/1B-light chain 3)의 생성이 증가되는 것을 알 수 있다. The results are shown in FIG. 1, and as can be seen from FIG. 1, the production of LC3-II (Microtubule-associated protein 1A/1B-light chain 3) is increased by the tryptamine derivative compound A-1 of the present invention. it can be seen that
[실험예 2] 화합물 A-1 및 A-2에 의한 항산화 활성능 분석[Experimental Example 2] Analysis of antioxidant activity by compounds A-1 and A-2
본 발명의 트립타민 유도체 화합물 A-1 및 A-2의 항산화 활성을 분석하기 위해 ABTS assay를 수행하였다. 구체적인 실험 방법으로 ABTS (2,2'-azino-bis (3-ethyl benzothiazoline-6-sulfonic acid)) 0.04 g, 과황산칼륨(Potassium persulfate) 0.007 g을 DW 5 mL에 녹여 ABTS solution을 만든 뒤 상온 암조건에 하룻밤(overnight)동안 두었다. 청록색으로 변한 ABTS solution을 PBS로 희석하여 O.D.를 1.5로 맞추었다. Trolox 1 mg/mL을 1/2씩 1/512까지, 비타민 C 및 화합물 A-1 1 mM을 1/2씩 1/128까지 DW에 희석하였다. 희석한 샘플, Trolox(standard), 비타민 C(양성대조군), DW(음성대조군)를 96-웰플레이트에 50 μL씩 분주하고, 희석한 ABTS solution 50 μL를 추가하였다. 30분간 상온 암조건에서 반응시키고 734 nm로 O.D.를 측정하였다. Trolox O.D.와 농도로 표준곡선(standard curve)를 그리고, 시료, 비타민 C의 O.D.값을 대입하여 각각의 TEAC(trolox equivalent antioxidant capacity; mmol/g)를 산출하였다.ABTS assay was performed to analyze the antioxidant activity of the tryptamine derivative compounds A-1 and A-2 of the present invention. As a specific experimental method, 0.04 g of ABTS (2,2'-azino-bis (3-ethyl benzothiazoline-6-sulfonic acid)) and 0.007 g of potassium persulfate are dissolved in 5 mL of DW to make ABTS solution, and then at room temperature It was placed overnight in dark conditions. The O.D. was adjusted to 1.5 by diluting the ABTS solution, which had turned blue-green, with PBS. 1 mg/mL of Trolox was diluted in DW by ½ to 1/512 and 1 mM vitamin C and compound A-1 to 1/128 in ½ aliquots. The diluted sample, Trolox (standard), vitamin C (positive control), and DW (negative control) were dispensed in a 96-well plate by 50 μL, and 50 μL of diluted ABTS solution was added. The reaction was carried out under dark conditions at room temperature for 30 minutes, and the O.D. was measured at 734 nm. A standard curve was drawn with the Trolox O.D. and the concentration, and the O.D. value of the sample and vitamin C was substituted to calculate the trolox equivalent antioxidant capacity (mmol/g) of each TEAC.
그 결과를 도 2에 나타내었으며, 도 2에서 알 수 있는 바와 같이, 본 발명의 트립타민 유도체 화합물 A-1을 처리한 경우에는 비타민 C보다 2.5~3배 가량 높은 항산화 활성을 가지는 것을 확인할 수 있었다. The results are shown in FIG. 2, and as can be seen from FIG. 2, when the tryptamine derivative compound A-1 of the present invention was treated, it was confirmed that the antioxidant activity was 2.5 to 3 times higher than that of vitamin C. .
[실험예 3] 화합물 A-1 및 A-2에 의한 항산화 단백질들의 발현 분석[Experimental Example 3] Expression analysis of antioxidant proteins by compounds A-1 and A-2
본 발명의 트립타민 유도체 화합물 A-1 및 A-2의 처리에 의한 세포 내 항산화 단백질 활성 증가를 분석하기 위해 SOD-1(Superoxide dismutase-1), Prx-1(peroxiredoxin)과 Prx-3(peroxiredoxin) 단백질, catalase 대한 웨스턴 블랏을 실험예 1과 동일한 방법으로 수행하였다. To analyze the increase in intracellular antioxidant protein activity by treatment with the tryptamine derivative compounds A-1 and A-2 of the present invention, SOD-1 (superoxide dismutase-1), Prx-1 (peroxiredoxin) and Prx-3 (peroxiredoxin) ) Western blot for protein and catalase was performed in the same manner as in Experimental Example 1.
그 결과를 도 3에 나타내었으며, 도 3에서 알 수 있는 바와 같이, 본 발명의 트립타민 유도체 화합물에 의해 SOD-1 단백질 발현이 증가되는 것을 알 수 있다. Prx-3 단백질의 발현은 대조구 대비하여 약하게 증가한 반면, Prx-2 단백질 및 Catalase 효소 단백질 발현은 높이 증가되는 것을 알 수 있다. The results are shown in FIG. 3 , and as can be seen from FIG. 3 , it can be seen that SOD-1 protein expression is increased by the tryptamine derivative compound of the present invention. It can be seen that the expression of Prx-3 protein is slightly increased compared to the control, whereas the expression of Prx-2 protein and Catalase enzyme protein is increased.
[실험예 4] 화합물 A-1 및 A-2에 의한 노화 단백질들의 발현 분석[Experimental Example 4] Expression analysis of senescent proteins by compounds A-1 and A-2
본 발명의 트립타민 유도체 화합물 A-1 및 A-2의 처리에 의한 세포 내 노화관련 단백질의 발현 감소를 분석하기 위해 p21(Cip1)과 p16(INK4a) 단백질에 대한 웨스턴 블랏을 수행하였다. Western blotting was performed on p21 (Cip1) and p16 (INK4a) proteins to analyze the decrease in the expression of senescence-related proteins in cells by treatment with the tryptamine derivative compounds A-1 and A-2 of the present invention.
사람섬유아세포인 HDF (Human dermal fibroblast)는 배양용 12-웰플레이트에 5 X 104 개의 세포 수로 일정하게 분주하여 DF-1 배지(Dermal Fibroblast Growth Medium, Zenbio)에서 48시간 동안 37℃, 5% CO2 조건으로 인큐베이터로 배양하였다. 산화 스트레스에 의한 세포 노화를 유도하기 위하여 10 μM의 화합물 A-1 및 200 μM의 과산화수소(H2O2)를 배양 후 48시간 후에 1차 동시 처리하였고, 24시간 후에 화합물 A-1 10 μM 와 200 μM의 과산화수소를 2차 동시 처리하였다. 화합물 처리 후 96시간 동안 배양하고, 배양 종료 후 배지를 제거한 후, 배양한 세포를 단백질 분해 억제제가 포함되어 있는 세포 용해 버퍼을 이용하여 용해시켰다. 상기 용해된 용액을 원심분리기를 이용하여 전체 용액을 분획한 뒤, 이하 단백질 발현을 분석하는 단계를 실험예 1과 동일하게 진행하였다. Human dermal fibroblasts (HDFs), which are human fibroblasts, were uniformly aliquoted at the number of 5 X 10 4 cells in a 12-well plate for culture and placed in DF-1 medium (Dermal Fibroblast Growth Medium, Zenbio) at 37°C, 5% for 48 hours. Incubated in an incubator under CO 2 conditions. In order to induce cellular senescence by oxidative stress, 10 μM of Compound A-1 and 200 μM of hydrogen peroxide (H 2 O 2 ) were first co-treated 48 hours after incubation, and 24 hours later, 10 μM of Compound A-1 and A second simultaneous treatment with 200 μM hydrogen peroxide was performed. After treatment with the compound, incubated for 96 hours, and after the culture was terminated, the medium was removed, and the cultured cells were lysed using a cell lysis buffer containing a proteolysis inhibitor. After fractionating the entire solution using a centrifuge from the dissolved solution, the steps of analyzing protein expression were performed in the same manner as in Experimental Example 1.
그 결과를 도 4에 나타내었으며, 도 4에서 알 수 있는 바와 같이, 본 발명의 트립타민 유도체 화합물 처리 시, 산화 스트레스에 의해 증가한 p21 및 p16 단백질 발현이 23% 내지 49% 수준으로 감소되는 것을 알 수 있다. The results are shown in FIG. 4, and as can be seen from FIG. 4, when the tryptamine derivative compound of the present invention is treated, the expression of p21 and p16 proteins increased by oxidative stress is reduced to a level of 23% to 49%. can
Claims (7)
[화학식 1]
상기 화학식 1에서,
R1 은 수소, 할로겐, C1-C10알킬, 또는 C1-C10알콕시이고;
L은 NH 또는 O이고;
R2는 C6-C20아릴, C3-C20헤테로아릴 또는 5원 내지 7원의 헤테로시클로알킬이고, 상기 R2의 아릴 및 헤테로아릴은 독립적으로 할로겐, C1-C10알킬, C1-C10알콕시, C1-C10알킬싸이오 또는 나이트릴로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있다.
An anti-aging composition comprising a tryptamine derivative compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]
In Formula 1,
R 1 is hydrogen, halogen, C1-C10 alkyl, or C1-C10 alkoxy;
L is NH or O;
R 2 is C6-C20 aryl, C3-C20 heteroaryl, or 5 to 7 membered heterocycloalkyl, and aryl and heteroaryl of R 2 are independently halogen, C1-C10 alkyl, C1-C10 alkoxy, C1- It may be further substituted with one or more selected from the group consisting of C10 alkylthio or nitrile.
상기 화학식 1에서 R1은 수소 또는 C1-C10알콕시이고; L은 NH이고; R2는 C6-C20아릴이고; 상기 R2의 아릴은 할로겐, C1-C10알킬, C1-C10알콕시, C1-C10알킬싸이오 및 나이트릴로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있는, 항노화용 조성물.
The method of claim 1,
In Formula 1, R 1 is hydrogen or C1-C10 alkoxy; L is NH; R 2 is C6-C20 aryl; The aryl of R 2 may be further substituted with one or more selected from the group consisting of halogen, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkylthio and nitrile.
상기 화학식 1에서 R1은 수소 또는 C1-C4알콕시이고; L은 NH이고; R2는 C6-C20아릴이고; 상기 R2의 아릴은 C1-C10알킬로 더 치환된, 항노화용 조성물.
The method of claim 1,
In Formula 1, R 1 is hydrogen or C1-C4 alkoxy; L is NH; R 2 is C6-C20 aryl; The aryl of R 2 is further substituted with C1-C10 alkyl, anti-aging composition.
상기 화학식 1로 표시되는 트립타민 유도체 화합물은 하기 화합물로부터 선택되는 것을 특징으로 하는 항노화용 조성물.
The method of claim 1,
The tryptamine derivative compound represented by Formula 1 is an anti-aging composition, characterized in that it is selected from the following compounds.
상기 화학식 1로 표시되는 트립타민 유도체 화합물은 하기 화합물로부터 선택되는 것을 특징으로 하는 항노화용 조성물.
The tryptamine derivative compound represented by Formula 1 is an anti-aging composition, characterized in that it is selected from the following compounds.
A cosmetic composition for anti-aging comprising the tryptamine derivative compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5 as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020210015323A KR102609067B1 (en) | 2021-02-03 | 2021-02-03 | Anti-aging composition comprising a tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020210015323A KR102609067B1 (en) | 2021-02-03 | 2021-02-03 | Anti-aging composition comprising a tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20220111915A true KR20220111915A (en) | 2022-08-10 |
| KR102609067B1 KR102609067B1 (en) | 2023-12-04 |
Family
ID=82846673
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020210015323A KR102609067B1 (en) | 2021-02-03 | 2021-02-03 | Anti-aging composition comprising a tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR102609067B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024054008A1 (en) | 2022-09-05 | 2024-03-14 | 주식회사 엘지에너지솔루션 | Apparatus and method for pairing batteries |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200095085A (en) * | 2019-01-31 | 2020-08-10 | (주)아모레퍼시픽 | Novel tryptamine azide derivative compounds and skin anti-inflammatory or anti-aging compositions comprising the same |
-
2021
- 2021-02-03 KR KR1020210015323A patent/KR102609067B1/en active IP Right Grant
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200095085A (en) * | 2019-01-31 | 2020-08-10 | (주)아모레퍼시픽 | Novel tryptamine azide derivative compounds and skin anti-inflammatory or anti-aging compositions comprising the same |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024054008A1 (en) | 2022-09-05 | 2024-03-14 | 주식회사 엘지에너지솔루션 | Apparatus and method for pairing batteries |
Also Published As
| Publication number | Publication date |
|---|---|
| KR102609067B1 (en) | 2023-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2010520233A (en) | Cosmetic composition for skin whitening containing arctin, arctigenin or a mixture thereof as an active ingredient | |
| US10662140B2 (en) | Method for skin-whitening using composition containing resveratryl triglycolate | |
| KR102609067B1 (en) | Anti-aging composition comprising a tryptamine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient | |
| KR102068635B1 (en) | 3,4,5-Trimethoxy cinnamic acid derivatives, preparation method thereof, and skin whithening composition comprising the same | |
| WO2012051741A1 (en) | Glycin derivatives inhibiting melanin production and whitening composition thereof | |
| KR20180033245A (en) | The novel selective 11-beta-hydroxysteroid dehydrogenase type 1 | |
| JP6692084B2 (en) | Skin whitening cosmetic composition | |
| KR102457475B1 (en) | Cosmetic and functional food composition comprising caffeoylmalic acid having whitening and anti-photoaging activities | |
| JP7054156B2 (en) | Tyrosinase inhibitor | |
| CN108368041B (en) | (R) -N- (adamantyl-2-yl) pyrrolidine-2-carboxamide derivatives for cosmetic use | |
| TWI308148B (en) | Novel compound of 6-methyl-3-phenethyl-3,4-dihydro-1h-quinazoline-2-thione, its preparation and a depigmentation composition containing the same as an effective component | |
| KR20130092367A (en) | Lignan compound derived from kadsura coccinea and method of obtaining thereof | |
| WO2019063710A1 (en) | Resorcinol derivatives for their cosmetic use | |
| KR102498762B1 (en) | Composition for anti-wrinkle effect comprising fermented product of Momordica charantia or compound isolated from therefrom as effective component | |
| KR100630905B1 (en) | Cosmetic composition comprising novel hydroxyaniline derivative salts | |
| KR102600558B1 (en) | Composition for promoting hair growth and preventing hair loss comprising atraric acid | |
| KR101695375B1 (en) | Composition for promoting hair growth and restoration comprising new derivatives of pantetheine | |
| KR102498763B1 (en) | Composition for improving skin whitening comprising fermented product of Momordica charantia or compound isolated therefrom as effective componenet | |
| KR102463237B1 (en) | Salicylic acid derivative compounds, preparation method thereof, and whitening cosmetic composition comprising the same | |
| JP5667774B2 (en) | Melanin production inhibitor, glutathione production promoter, hyaluronic acid production promoter, involucrin production promoter, and skin cosmetics | |
| KR20190053534A (en) | Idebenone derivative compound and cosmetic composition comprising the same | |
| KR101693034B1 (en) | Skin Whitening Composition Comprising Caffeic Acid Derivatives as the Active Ingredients | |
| JP2019531275A (en) | Skin anti-aging composition comprising dehydrogenated abietic acid and compound K | |
| US10376453B1 (en) | Composition for promoting hair growth containing novel pantetheine derivative | |
| KR101586055B1 (en) | COMPOSITION FOR IMPROVING SKIN WHITENING COMPRISING 4-(β-D-GLUCOPYRANOSYLOXY)-1,5-NAPHTHALENEDIOL AS EFFECTIVE COMPONENT |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E902 | Notification of reason for refusal | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant |