JP5529280B2 - 癌治療用のジ（フェニルプロパノイド）・グリセロール誘導体 - Google Patents
癌治療用のジ（フェニルプロパノイド）・グリセロール誘導体 Download PDFInfo
- Publication number
- JP5529280B2 JP5529280B2 JP2012532432A JP2012532432A JP5529280B2 JP 5529280 B2 JP5529280 B2 JP 5529280B2 JP 2012532432 A JP2012532432 A JP 2012532432A JP 2012532432 A JP2012532432 A JP 2012532432A JP 5529280 B2 JP5529280 B2 JP 5529280B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- alkoxy
- pharmaceutically acceptable
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 39
- 201000011510 cancer Diseases 0.000 title claims description 35
- 238000011282 treatment Methods 0.000 title description 6
- 229930015704 phenylpropanoid Natural products 0.000 title 1
- 150000002995 phenylpropanoid derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 100
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- -1 (E) -3- (3,4-dimethoxyphenyl) acryloyl Chemical group 0.000 claims description 36
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 3
- 230000002147 killing effect Effects 0.000 claims description 3
- 230000006907 apoptotic process Effects 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 73
- 239000000203 mixture Substances 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 150000005690 diesters Chemical class 0.000 description 14
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 208000029742 colonic neoplasm Diseases 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 206010009944 Colon cancer Diseases 0.000 description 11
- 230000001093 anti-cancer Effects 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical class OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000012876 carrier material Substances 0.000 description 8
- 150000001851 cinnamic acid derivatives Chemical class 0.000 description 8
- JUVGLPRIQOJMIR-UHFFFAOYSA-N oxiran-2-ylmethyl 3-phenylprop-2-enoate Chemical class C=1C=CC=CC=1C=CC(=O)OCC1CO1 JUVGLPRIQOJMIR-UHFFFAOYSA-N 0.000 description 8
- NGSWKAQJJWESNS-ZZXKWVIFSA-N trans-4-coumaric acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C=C1 NGSWKAQJJWESNS-ZZXKWVIFSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- HJBWJAPEBGSQPR-GQCTYLIASA-N 3,4-dimethoxycinnamic acid Chemical compound COC1=CC=C(\C=C\C(O)=O)C=C1OC HJBWJAPEBGSQPR-GQCTYLIASA-N 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- 206010060862 Prostate cancer Diseases 0.000 description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 6
- 208000032839 leukemia Diseases 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- FBSFWRHWHYMIOG-UHFFFAOYSA-N methyl 3,4,5-trihydroxybenzoate Chemical compound COC(=O)C1=CC(O)=C(O)C(O)=C1 FBSFWRHWHYMIOG-UHFFFAOYSA-N 0.000 description 6
- 235000013824 polyphenols Nutrition 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical class [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 6
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 5
- HJBWJAPEBGSQPR-UHFFFAOYSA-N DMCA Natural products COC1=CC=C(C=CC(O)=O)C=C1OC HJBWJAPEBGSQPR-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 206010033128 Ovarian cancer Diseases 0.000 description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 5
- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 208000000453 Skin Neoplasms Diseases 0.000 description 4
- 235000004883 caffeic acid Nutrition 0.000 description 4
- 229940074360 caffeic acid Drugs 0.000 description 4
- 235000013985 cinnamic acid Nutrition 0.000 description 4
- 229930016911 cinnamic acid Natural products 0.000 description 4
- QAIPRVGONGVQAS-UHFFFAOYSA-N cis-caffeic acid Natural products OC(=O)C=CC1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- LDBPIZIYTBIRPM-VQHVLOKHSA-N phenyl (e)-3-(3,4-dihydroxyphenyl)prop-2-enoate Chemical compound C1=C(O)C(O)=CC=C1\C=C\C(=O)OC1=CC=CC=C1 LDBPIZIYTBIRPM-VQHVLOKHSA-N 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- IWHVCHNCTHGORM-UHDJGPCESA-M potassium;(e)-3-phenylprop-2-enoate Chemical compound [K+].[O-]C(=O)\C=C\C1=CC=CC=C1 IWHVCHNCTHGORM-UHDJGPCESA-M 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 201000000849 skin cancer Diseases 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- AFDXODALSZRGIH-QPJJXVBHSA-N (E)-3-(4-methoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=C(\C=C\C(O)=O)C=C1 AFDXODALSZRGIH-QPJJXVBHSA-N 0.000 description 3
- HGDZRSNJGRIAKS-GQCTYLIASA-N (e)-3-(3,4-dimethoxyphenyl)prop-2-enoyl chloride Chemical compound COC1=CC=C(\C=C\C(Cl)=O)C=C1OC HGDZRSNJGRIAKS-GQCTYLIASA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- RURZKIPNBNXRHB-UHFFFAOYSA-N C1=CC=C(C=C1)C=C(CCCC(=CC2=CC=CC=C2)C(=O)O)C(=O)O Chemical class C1=CC=C(C=C1)C=C(CCCC(=CC2=CC=CC=C2)C(=O)O)C(=O)O RURZKIPNBNXRHB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- RXGCYMALDZSJSS-YZQSPKDBSA-N [3-[3-(3,4-dihydroxyphenyl)prop-2-enoyloxy]-2-hydroxypropyl] (E)-3-phenylprop-2-enoate Chemical compound C=1C=C(O)C(O)=CC=1C=CC(=O)OCC(O)COC(=O)\C=C\C1=CC=CC=C1 RXGCYMALDZSJSS-YZQSPKDBSA-N 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 229940034982 antineoplastic agent Drugs 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- IBKQQKPQRYUGBJ-UHFFFAOYSA-N methyl gallate Natural products CC(=O)C1=CC(O)=C(O)C(O)=C1 IBKQQKPQRYUGBJ-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000003444 phase transfer catalyst Substances 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- BROPJIXYPBXFSL-UHFFFAOYSA-M potassium;3-(4-hydroxyphenyl)prop-2-enoate Chemical compound [K+].OC1=CC=C(C=CC([O-])=O)C=C1 BROPJIXYPBXFSL-UHFFFAOYSA-M 0.000 description 3
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- COJAJMNJKIUMOT-DUXPYHPUSA-N (e)-3-(3,4-dihydroxyphenyl)prop-2-enoyl chloride Chemical compound OC1=CC=C(\C=C\C(Cl)=O)C=C1O COJAJMNJKIUMOT-DUXPYHPUSA-N 0.000 description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 2
- MFFCZSWTQMCKFP-OWOJBTEDSA-N 3,5-dihydroxycinnamic acid Chemical class OC(=O)\C=C\C1=CC(O)=CC(O)=C1 MFFCZSWTQMCKFP-OWOJBTEDSA-N 0.000 description 2
- NGSWKAQJJWESNS-UHFFFAOYSA-N 4-coumaric acid Chemical compound OC(=O)C=CC1=CC=C(O)C=C1 NGSWKAQJJWESNS-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 244000163122 Curcuma domestica Species 0.000 description 2
- 235000003392 Curcuma domestica Nutrition 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 208000001382 Experimental Melanoma Diseases 0.000 description 2
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 241000241413 Propolis Species 0.000 description 2
- GRZQNEYQRVPNRY-WUZDHUPESA-N [(e)-3-phenylprop-2-enyl] (e)-3-(3,4-dihydroxyphenyl)prop-2-enoate Chemical compound C1=C(O)C(O)=CC=C1\C=C\C(=O)OC\C=C\C1=CC=CC=C1 GRZQNEYQRVPNRY-WUZDHUPESA-N 0.000 description 2
- IEKFHRRAYZRAIJ-BTWZHFOESA-N [3-[3-(3,4-dimethoxyphenyl)prop-2-enoyloxy]-2-hydroxypropyl] (e)-3-phenylprop-2-enoate Chemical compound C1=C(OC)C(OC)=CC=C1C=CC(=O)OCC(O)COC(=O)\C=C\C1=CC=CC=C1 IEKFHRRAYZRAIJ-BTWZHFOESA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001266 acyl halides Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000005215 alkyl ethers Chemical class 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- WWVKQTNONPWVEL-VQHVLOKHSA-N benzyl (e)-3-(3,4-dihydroxyphenyl)prop-2-enoate Chemical compound C1=C(O)C(O)=CC=C1\C=C\C(=O)OCC1=CC=CC=C1 WWVKQTNONPWVEL-VQHVLOKHSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- WWVKQTNONPWVEL-UHFFFAOYSA-N caffeic acid phenethyl ester Natural products C1=C(O)C(O)=CC=C1C=CC(=O)OCC1=CC=CC=C1 WWVKQTNONPWVEL-UHFFFAOYSA-N 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- GRZQNEYQRVPNRY-UHFFFAOYSA-N cinnamyl caffeate Natural products C1=C(O)C(O)=CC=C1C=CC(=O)OCC=CC1=CC=CC=C1 GRZQNEYQRVPNRY-UHFFFAOYSA-N 0.000 description 2
- 229940126142 compound 16 Drugs 0.000 description 2
- WBCMGDNFDRNGGZ-ACNVUDSMSA-N coumarate Natural products COC(=O)C1=CO[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H]3[C@@H]1C=C[C@]34OC(=O)C(=C4)[C@H](C)OC(=O)C=Cc5ccc(O)cc5 WBCMGDNFDRNGGZ-ACNVUDSMSA-N 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 235000003373 curcuma longa Nutrition 0.000 description 2
- 235000012754 curcumin Nutrition 0.000 description 2
- 229940109262 curcumin Drugs 0.000 description 2
- 239000004148 curcumin Substances 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- SWUARLUWKZWEBQ-VQHVLOKHSA-N phenethyl caffeate Chemical compound C1=C(O)C(O)=CC=C1\C=C\C(=O)OCCC1=CC=CC=C1 SWUARLUWKZWEBQ-VQHVLOKHSA-N 0.000 description 2
- SWUARLUWKZWEBQ-UHFFFAOYSA-N phenylethyl ester of caffeic acid Natural products C1=C(O)C(O)=CC=C1C=CC(=O)OCCC1=CC=CC=C1 SWUARLUWKZWEBQ-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 229940069949 propolis Drugs 0.000 description 2
- WZXKPNYMUZGZIA-RMKNXTFCSA-N propyl (e)-3-(4-methoxyphenyl)prop-2-enoate Chemical compound CCCOC(=O)\C=C\C1=CC=C(OC)C=C1 WZXKPNYMUZGZIA-RMKNXTFCSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000012066 reaction slurry Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- SDBVEUJRZKHWSH-VEELZWTKSA-M sodium (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate Chemical compound [Na+].OC1=CC=C(\C=C\C([O-])=O)C=C1O SDBVEUJRZKHWSH-VEELZWTKSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 235000013976 turmeric Nutrition 0.000 description 2
- NITWSHWHQAQBAW-QPJJXVBHSA-N (E)-4-coumaric acid methyl ester Chemical compound COC(=O)\C=C\C1=CC=C(O)C=C1 NITWSHWHQAQBAW-QPJJXVBHSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- LLHUCTVDBMDKQP-UHFFFAOYSA-N 3-(3-phenylprop-2-enoyloxy)propyl 3-phenylprop-2-enoate Chemical class C=1C=CC=CC=1C=CC(=O)OCCCOC(=O)C=CC1=CC=CC=C1 LLHUCTVDBMDKQP-UHFFFAOYSA-N 0.000 description 1
- NGSWKAQJJWESNS-ZZXKWVIFSA-M 4-Hydroxycinnamate Natural products OC1=CC=C(\C=C\C([O-])=O)C=C1 NGSWKAQJJWESNS-ZZXKWVIFSA-M 0.000 description 1
- DFYRUELUNQRZTB-UHFFFAOYSA-N Acetovanillone Natural products COC1=CC(C(C)=O)=CC=C1O DFYRUELUNQRZTB-UHFFFAOYSA-N 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 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
- DGAKHGXRMXWHBX-ONEGZZNKSA-N Azoxymethane Chemical compound C\N=[N+](/C)[O-] DGAKHGXRMXWHBX-ONEGZZNKSA-N 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241001337225 Daucus carota subsp. carota Species 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 241000196324 Embryophyta Species 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
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-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
- 102000003820 Lipoxygenases Human genes 0.000 description 1
- 108090000128 Lipoxygenases Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 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
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930182558 Sterol Chemical class 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000005233 alkylalcohol group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 208000002352 blister Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- MAEVSPLUELJOMM-UHFFFAOYSA-N caffeic acid methyl ester Natural products COC(=O)C=CC1=CC=C(O)C=C1O MAEVSPLUELJOMM-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Chemical class 0.000 description 1
- 229920002678 cellulose Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- ZAOVCWMXSBNHBU-UHFFFAOYSA-N chromium;pyridine;hydrochloride Chemical compound Cl.[Cr].C1=CC=NC=C1 ZAOVCWMXSBNHBU-UHFFFAOYSA-N 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 230000004736 colon carcinogenesis Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000013211 curve analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- 235000004515 gallic 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
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- NOQAMNANIGSRAX-UHFFFAOYSA-N methyl 3-(3,5-dihydroxyphenyl)prop-2-enoate Chemical compound COC(=O)C=CC1=CC(O)=CC(O)=C1 NOQAMNANIGSRAX-UHFFFAOYSA-N 0.000 description 1
- OCNYGKNIVPVPPX-HWKANZROSA-N methyl caffeate Chemical compound COC(=O)\C=C\C1=CC=C(O)C(O)=C1 OCNYGKNIVPVPPX-HWKANZROSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- VJMRKWPMFQGIPI-UHFFFAOYSA-N n-(2-hydroxyethyl)-5-(hydroxymethyl)-3-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide Chemical class OCC1=C(C(=O)NCCO)C(C)=NN1C1=CC=CC2=C1SC(CC=1C=C(C=CC=1)C(F)(F)F)=C2 VJMRKWPMFQGIPI-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920001223 polyethylene glycol Chemical class 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- OXZXWAVRVVBHJJ-UHFFFAOYSA-M potassium 3-(3,4-dimethoxyphenyl)prop-2-enoate Chemical compound [K+].COC1=CC=C(C=CC([O-])=O)C=C1OC OXZXWAVRVVBHJJ-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 125000003198 secondary alcohol group Chemical group 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- KKSDGJDHHZEWEP-SNAWJCMRSA-N trans-3-coumaric acid Chemical class OC(=O)\C=C\C1=CC=CC(O)=C1 KKSDGJDHHZEWEP-SNAWJCMRSA-N 0.000 description 1
- QAIPRVGONGVQAS-DUXPYHPUSA-M trans-caffeate Chemical compound OC1=CC=C(\C=C\C([O-])=O)C=C1O QAIPRVGONGVQAS-DUXPYHPUSA-M 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/16—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by esterified hydroxyl radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25028709P | 2009-10-09 | 2009-10-09 | |
| US61/250,287 | 2009-10-09 | ||
| PCT/CA2010/001613 WO2011041907A1 (en) | 2009-10-09 | 2010-10-08 | Derivatives of di(phenylpropanoid) glycerol for the treatment of cancer |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013507327A JP2013507327A (ja) | 2013-03-04 |
| JP2013507327A5 JP2013507327A5 (enExample) | 2013-11-21 |
| JP5529280B2 true JP5529280B2 (ja) | 2014-06-25 |
Family
ID=43352967
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012532432A Expired - Fee Related JP5529280B2 (ja) | 2009-10-09 | 2010-10-08 | 癌治療用のジ（フェニルプロパノイド）・グリセロール誘導体 |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US9061993B2 (enExample) |
| EP (1) | EP2486026B1 (enExample) |
| JP (1) | JP5529280B2 (enExample) |
| CN (1) | CN102264713A (enExample) |
| BR (1) | BR112012008204A2 (enExample) |
| CA (1) | CA2715662C (enExample) |
| CY (1) | CY1123161T1 (enExample) |
| DK (1) | DK2486026T3 (enExample) |
| ES (1) | ES2810906T3 (enExample) |
| HR (1) | HRP20201217T1 (enExample) |
| HU (1) | HUE051549T2 (enExample) |
| LT (1) | LT2486026T (enExample) |
| MX (1) | MX360417B (enExample) |
| MY (2) | MY160378A (enExample) |
| PL (1) | PL2486026T3 (enExample) |
| PT (1) | PT2486026T (enExample) |
| RS (1) | RS60667B1 (enExample) |
| SI (1) | SI2486026T1 (enExample) |
| SM (1) | SMT202000428T1 (enExample) |
| WO (1) | WO2011041907A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8907117B2 (en) * | 2011-09-08 | 2014-12-09 | Henry Lowe | Anti-tumor and anti-inflammatory dicinnamoyl-glycerol esters and their analogues |
| US20160106722A1 (en) | 2014-10-21 | 2016-04-21 | Life Plus, LLC | Human therapeutic agents |
| US9907786B2 (en) | 2014-10-21 | 2018-03-06 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing harmine and isovanillin components, and methods of use thereof |
| US10092550B2 (en) | 2014-10-21 | 2018-10-09 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing curcumin, harmine, and isovanillin components, and methods of use thereof |
| US12129265B2 (en) | 2020-07-21 | 2024-10-29 | Ankh Life Sciences Limited | Therapeutic agents and uses thereof |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3857873A (en) * | 1974-02-11 | 1974-12-31 | Warner Lambert Co | 3-hydroxy-5-(3-(substituted-amino)-2-hydroxypropoxy)-benzyl alcohols |
| CH648753A5 (de) * | 1981-07-22 | 1985-04-15 | Givaudan & Cie Sa | Lichtschutzmittel. |
| CN1238333C (zh) * | 2003-06-18 | 2006-01-25 | 清华大学 | 药物化合物菠萝酰酯及其制备方法和用途 |
| US7713556B2 (en) * | 2006-12-08 | 2010-05-11 | Henry Lowe | Anti-tumor and anti-inflammatory extracts of plant biomass and their uses |
| AU2008205312B2 (en) * | 2007-01-08 | 2013-11-21 | Annji Pharmaceutical Co., Ltd. | Compounds with (substituted phenyl)-propenal moiety, their derivatives, biological activity, and uses thereof |
| TWI383251B (zh) * | 2008-01-16 | 2013-01-21 | Eternal Chemical Co Ltd | 感光型聚醯亞胺 |
| KR101074149B1 (ko) * | 2009-04-15 | 2011-10-17 | 한밭대학교 산학협력단 | 신규 폴리페놀/폴리페놀 컨쥬게이트 화합물 및 그의 용도 |
| US8907117B2 (en) * | 2011-09-08 | 2014-12-09 | Henry Lowe | Anti-tumor and anti-inflammatory dicinnamoyl-glycerol esters and their analogues |
-
2010
- 2010-10-08 CN CN201080003781XA patent/CN102264713A/zh active Pending
- 2010-10-08 BR BR112012008204A patent/BR112012008204A2/pt not_active Application Discontinuation
- 2010-10-08 MY MYPI2012001601A patent/MY160378A/en unknown
- 2010-10-08 CA CA2715662A patent/CA2715662C/en active Active
- 2010-10-08 MY MYPI2016000361A patent/MY187188A/en unknown
- 2010-10-08 SI SI201032026T patent/SI2486026T1/sl unknown
- 2010-10-08 ES ES10821532T patent/ES2810906T3/es active Active
- 2010-10-08 DK DK10821532.8T patent/DK2486026T3/da active
- 2010-10-08 HU HUE10821532A patent/HUE051549T2/hu unknown
- 2010-10-08 PL PL10821532T patent/PL2486026T3/pl unknown
- 2010-10-08 WO PCT/CA2010/001613 patent/WO2011041907A1/en not_active Ceased
- 2010-10-08 SM SM20200428T patent/SMT202000428T1/it unknown
- 2010-10-08 PT PT108215328T patent/PT2486026T/pt unknown
- 2010-10-08 EP EP10821532.8A patent/EP2486026B1/en active Active
- 2010-10-08 MX MX2012004160A patent/MX360417B/es active IP Right Grant
- 2010-10-08 LT LTEP10821532.8T patent/LT2486026T/lt unknown
- 2010-10-08 RS RS20200931A patent/RS60667B1/sr unknown
- 2010-10-08 US US12/901,113 patent/US9061993B2/en active Active
- 2010-10-08 JP JP2012532432A patent/JP5529280B2/ja not_active Expired - Fee Related
- 2010-10-08 HR HRP20201217TT patent/HRP20201217T1/hr unknown
-
2015
- 2015-05-17 US US14/714,318 patent/US10052301B2/en active Active
-
2020
- 2020-08-05 CY CY20201100724T patent/CY1123161T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX360417B (es) | 2018-10-25 |
| CN102264713A (zh) | 2011-11-30 |
| US20110086912A1 (en) | 2011-04-14 |
| JP2013507327A (ja) | 2013-03-04 |
| RS60667B1 (sr) | 2020-09-30 |
| CA2715662C (en) | 2013-05-07 |
| US20150246014A1 (en) | 2015-09-03 |
| MX2012004160A (es) | 2012-09-07 |
| US10052301B2 (en) | 2018-08-21 |
| BR112012008204A2 (pt) | 2017-07-18 |
| HUE051549T2 (hu) | 2021-10-28 |
| EP2486026A1 (en) | 2012-08-15 |
| PT2486026T (pt) | 2020-08-21 |
| SI2486026T1 (sl) | 2020-10-30 |
| US9061993B2 (en) | 2015-06-23 |
| EP2486026B1 (en) | 2020-06-24 |
| SMT202000428T1 (it) | 2020-09-10 |
| MY187188A (en) | 2021-09-09 |
| CA2715662A1 (en) | 2010-12-14 |
| MY160378A (en) | 2017-03-15 |
| PL2486026T3 (pl) | 2020-11-02 |
| DK2486026T3 (da) | 2020-08-17 |
| WO2011041907A1 (en) | 2011-04-14 |
| CY1123161T1 (el) | 2021-10-29 |
| ES2810906T3 (es) | 2021-03-09 |
| LT2486026T (lt) | 2020-09-10 |
| HRP20201217T1 (hr) | 2020-12-11 |
| EP2486026A4 (en) | 2015-07-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2007270951B2 (en) | Dioxo-alkanes and dioxo-alkenes | |
| US5736576A (en) | Method of treating malignant tumors with thyroxine analogues having no significant hormonal activity | |
| Lin et al. | Antitumor agents 247. New 4-ethoxycarbonylethyl curcumin analogs as potential antiandrogenic agents | |
| US20100094041A1 (en) | Anti-inflammatory and psoriasis treatment and protein kinase inhibition by hydroxy stilbenes and novel stilbene derivatives and analogues | |
| JP5529280B2 (ja) | 癌治療用のジ（フェニルプロパノイド）・グリセロール誘導体 | |
| PT1412317E (pt) | Derivados retinóides com actividades anti-angiogénica, anti-tumoral e pró-apoptótica | |
| US20090075943A1 (en) | Combretastatin Analogs with Tubulin Binding Activity | |
| Mourad et al. | Novel HDAC/tubulin dual inhibitor: Design, synthesis and docking studies of α-phthalimido-chalcone hybrids as potential anticancer agents with apoptosis-inducing activity | |
| Li et al. | Discovery of oral-available resveratrol-caffeic acid based hybrids inhibiting acetylated and phosphorylated STAT3 protein | |
| EP1284952A1 (en) | Substituted chalcones as therapeutic compounds | |
| JP2004517033A (ja) | 選択的エストロゲン受容体モジュレータとしてのハロゲン化トリフェニルエチレン誘導体 | |
| KR101975299B1 (ko) | 인돌아세트산의 코어구조를 함유하는 화합물 및 그의 용도 | |
| US20070191627A1 (en) | Stilbene derivatives and their use in medicaments | |
| TW455575B (en) | Novel 7-aryl-6(Z)-heptatrienoic acid retinamides | |
| EP1268387B1 (en) | Specific salt forms of triphenylethylene derivatives as selective estrogen receptor modulators | |
| JP2002518506A (ja) | アリールスルホンアニリドホスフェート | |
| CA2980221C (en) | Indole analogs as 5-oxo-ete receptor antagonists and method of use thereof | |
| US5397802A (en) | Gem-dichlorocyclopropanes as antitumor agents | |
| JPH0519549B2 (enExample) | ||
| HK1164842A (en) | Derivatives of di(phenylpropanoid) glycerol for the treatment of cancer | |
| US8633242B2 (en) | Benzylidene indanones and processes for preparation and use thereof | |
| EP3322687B1 (en) | 2-benzyl-indanone compounds as anticancer agent and a process for preparation thereof | |
| CN1948275B (zh) | 白藜芦醇Mannich碱衍生物及其制备方法和用途 | |
| WO2025029660A9 (en) | Compounds with selectivity for certain cancers | |
| BRPI0803375A2 (pt) | compostos derivados de 4-hidroxi-3-metoxi-benzaldeìdo, processo de obtenção, composição farmacêutica, uso de um ou mais compostos |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130930 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130930 |
|
| A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20130930 |
|
| A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20131029 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131105 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140204 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20140204 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140204 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140318 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140416 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5529280 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |