CN111943830B - 一种新的二苯甲酮类化合物及其制备方法和应用 - Google Patents
一种新的二苯甲酮类化合物及其制备方法和应用 Download PDFInfo
- Publication number
- CN111943830B CN111943830B CN202010843889.5A CN202010843889A CN111943830B CN 111943830 B CN111943830 B CN 111943830B CN 202010843889 A CN202010843889 A CN 202010843889A CN 111943830 B CN111943830 B CN 111943830B
- Authority
- CN
- China
- Prior art keywords
- dihydroxyphenyl
- methyl
- trihydroxyphenyl
- butenyl
- methanone
- 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.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- -1 benzophenone compound Chemical class 0.000 title claims abstract description 13
- 239000012965 benzophenone Substances 0.000 title claims abstract description 12
- WEZRLAHIDFEGJL-UHFFFAOYSA-N (2,4-dihydroxyphenyl)-[3,4,5-trihydroxy-2,6-bis(3-methylbut-2-enyl)phenyl]methanone Chemical compound OC1=C(C=CC(=C1)O)C(=O)C1=C(C(=C(C(=C1CC=C(C)C)O)O)O)CC=C(C)C WEZRLAHIDFEGJL-UHFFFAOYSA-N 0.000 claims abstract description 37
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 22
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 16
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 13
- 230000000694 effects Effects 0.000 claims abstract description 13
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 11
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 7
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 7
- 229940079593 drug Drugs 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 18
- 102100024295 Maltase-glucoamylase Human genes 0.000 claims description 14
- 108010028144 alpha-Glucosidases Proteins 0.000 claims description 14
- HNVRRHSXBLFLIG-UHFFFAOYSA-N 3-hydroxy-3-methylbut-1-ene Chemical compound CC(C)(O)C=C HNVRRHSXBLFLIG-UHFFFAOYSA-N 0.000 claims description 13
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- WXVVTEIKTFLYCK-UHFFFAOYSA-N (2,4-dihydroxyphenyl)-(3,4,5-trihydroxyphenyl)methanone Chemical compound OC1=CC(O)=CC=C1C(=O)C1=CC(O)=C(O)C(O)=C1 WXVVTEIKTFLYCK-UHFFFAOYSA-N 0.000 claims description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- BZAZNULYLRVMSW-UHFFFAOYSA-N 2-Methyl-2-buten-3-ol Natural products CC(C)=C(C)O BZAZNULYLRVMSW-UHFFFAOYSA-N 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000004237 preparative chromatography Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 abstract description 15
- 230000000259 anti-tumor effect Effects 0.000 abstract description 7
- 239000002537 cosmetic Substances 0.000 abstract description 5
- 230000036541 health Effects 0.000 abstract description 5
- 239000003242 anti bacterial agent Substances 0.000 abstract description 4
- 102000005744 Glycoside Hydrolases Human genes 0.000 abstract description 2
- 108010031186 Glycoside Hydrolases Proteins 0.000 abstract description 2
- 229940125904 compound 1 Drugs 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 23
- 150000001875 compounds Chemical class 0.000 description 20
- 230000000052 comparative effect Effects 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 239000000243 solution Substances 0.000 description 11
- 235000006708 antioxidants Nutrition 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 235000014676 Phragmites communis Nutrition 0.000 description 6
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-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
- 230000009471 action Effects 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 3
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229960001285 quercetin Drugs 0.000 description 3
- 235000005875 quercetin Nutrition 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 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 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XDPLEXVZAXWIOI-UHFFFAOYSA-N (2-hydroxy-3,5-dimethylphenyl)-(3-hydroxy-4-methoxyphenyl)methanone Chemical compound CC=1C(=C(C=C(C=1)C)C(=O)C1=CC(=C(C=C1)OC)O)O XDPLEXVZAXWIOI-UHFFFAOYSA-N 0.000 description 2
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 2
- 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
- CSCPPACGZOOCGX-MICDWDOJSA-N 1-deuteriopropan-2-one Chemical compound [2H]CC(C)=O CSCPPACGZOOCGX-MICDWDOJSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 239000004107 Penicillin G sodium Substances 0.000 description 2
- 230000002292 Radical scavenging effect Effects 0.000 description 2
- WGCOQYDRMPFAMN-ZDUSSCGKSA-N [(3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-pyrimidin-5-ylmethanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CCC1)C(=O)C=1C=NC=NC=1 WGCOQYDRMPFAMN-ZDUSSCGKSA-N 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 229960000484 ceftazidime Drugs 0.000 description 2
- NMVPEQXCMGEDNH-TZVUEUGBSA-N ceftazidime pentahydrate Chemical compound O.O.O.O.O.S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC(C)(C)C(O)=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 NMVPEQXCMGEDNH-TZVUEUGBSA-N 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- MGJZITXUQXWAKY-UHFFFAOYSA-N diphenyl-(2,4,6-trinitrophenyl)iminoazanium Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1N=[N+](C=1C=CC=CC=1)C1=CC=CC=C1 MGJZITXUQXWAKY-UHFFFAOYSA-N 0.000 description 2
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000031700 light absorption Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 235000019369 penicillin G sodium Nutrition 0.000 description 2
- 229940056360 penicillin g Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000001424 substituent group Chemical group 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
- NNRJREJZWAFVPO-UHFFFAOYSA-N (2-hydroxy-3,5-dimethylphenyl)-(4-hydroxyphenyl)methanone Chemical compound OC1=CC=C(C=C1)C(=O)C1=C(C(=CC(=C1)C)C)O NNRJREJZWAFVPO-UHFFFAOYSA-N 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241001138501 Salmonella enterica Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000001136 chorion Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000007760 free radical scavenging Effects 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
- 125000002350 geranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- AJDUTMFFZHIJEM-UHFFFAOYSA-N n-(9,10-dioxoanthracen-1-yl)-4-[4-[[4-[4-[(9,10-dioxoanthracen-1-yl)carbamoyl]phenyl]phenyl]diazenyl]phenyl]benzamide Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C=CC=C2NC(=O)C(C=C1)=CC=C1C(C=C1)=CC=C1N=NC(C=C1)=CC=C1C(C=C1)=CC=C1C(=O)NC1=CC=CC2=C1C(=O)C1=CC=CC=C1C2=O AJDUTMFFZHIJEM-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000011345 viscous material Substances 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
- 238000005406 washing Methods 0.000 description 1
- 239000001043 yellow dye Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/82—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups
- C07C49/835—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups having unsaturation outside an aromatic ring
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
- A01N35/04—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing aldehyde or keto groups, or thio analogues thereof, directly attached to an aromatic ring system, e.g. acetophenone; Derivatives thereof, e.g. acetals
-
- 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
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Food Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Obesity (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Biochemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Endocrinology (AREA)
- Polymers & Plastics (AREA)
- Agronomy & Crop Science (AREA)
- Plant Pathology (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明提供了一种新的二苯甲酮类化合物，(2,4‑二羟基苯基)(2,6‑二(3‑甲基‑2‑丁烯基)‑3,4,5‑三羟基苯基)甲酮及其制备方法和应用，其结构如下化学式(Ⅰ)所示：
Description
技术领域
本发明涉及生化医药领域，具体涉及一种新的二苯甲酮类化合物，(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮及其制备方法和应用。
背景技术
二苯甲酮类化合物的母体结构为两个苯环分别连在一个羰基的两侧。两个苯环与羰基形成一个大的共轭体系。苯环上取代基的种类和位置会显著影响其生物活性。这类化合物的常见取代基有羟基、甲氧基、3-甲基2-丁烯基和香叶基等。其中，羟基可以增大分子的水溶性且可以和受体形成分子间氢键。因此，羟基对其生物活性具有显著的影响。如申请号201910371264.0的专利：一种羟基取代的二苯甲酮类化合物及其制备方法和应用，该中国专利公开了一种新的化合物(4-羟基苯基)(3,5-二甲基-2-羟基苯基)甲酮的制备方法及其在制备抗肿瘤药物上和在抑制酪氨酸酶活性上的应用。以及申请号为202010311435.3的专利(4-甲氧基-3-羟基苯基)(3,5-二甲基-2-羟基苯基)甲酮及制备方法和应用，该中国专利公开了一种新的化合物(4-甲氧基-3-羟基苯基)(3,5-二甲基-2-羟基苯基)甲酮的制备方法以及其在制备抗肿瘤药物方面的应用。
而(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮及其制备方法和应用并未被国内外文献及专利公开。
发明内容
为此，本发明的目的是提供一种具有一定的生理及药理活性的二苯甲酮类化合物。为实现本发明的目的，本发明采用了如下技术方案：
本发明的第一方面，提供了一种新的二苯甲酮类化合物，(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮，其结构如化学式(Ⅰ)所示：
本发明的第二方面，提供了(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的制备方法,包括：(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮在无水1,4-二氧六环、三氟化硼乙醚和2-甲基-3-丁烯-2-醇体系中反应，(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮含三个酚羟基的苯基被两个3-甲基-2-丁烯基取代，生成(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的过程，其反应式如下：
进一步地，所述(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮、三氟化硼乙醚与2-甲基-3-丁烯-2-醇的摩尔比为1：3：3。
而所述无水1,4-二氧六环仅作为溶剂，不参与(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的化学合成，其加入量可根据反应物的浓度进行调整。
进一步地，包括以下步骤：
将(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮、无水1,4-二氧六环和三氟化硼乙醚依次加入反应容器中，搅拌使其溶解后；滴加2-甲基-3-丁烯-2-醇，50-70℃反应20-40min；反应完毕，将反应液倒入水中，析出粘稠物，萃取，合并有机相，干燥，得到初产物；
将初产物用中压制备色谱分离纯化，得到(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮。
本发明的第三方面，提供了(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在制备抗肿瘤药物方面的应用，所述肿瘤包括白血病HL-60、肝癌SMMC-7721、乳腺癌MCF-7和结肠癌SW480。
本发明的第四方面，提供了(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在抗氧化方面的应用。
本发明的第五方面，提供了(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在抑制金黄色葡萄球菌ATCC29213活性方面的应用。
本发明的第六方面，提供了(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在抑制α-葡萄糖苷酶活性方面的应用。
本发明的第七方面，提供了(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在制备治疗糖尿病的药物方面的应用。
本发明所提供的式Ⅰ所示化合物(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮，为一种新的二苯甲酮类化合物，对人类的肝和肺的正常细胞的毒性较小，具有抑制肿瘤细胞生成的效果，具有明显的抗肿瘤活性，可用于制备抗肿瘤药物；还具有较强的抗氧化活性，可用于制备抗氧化的药物、保健品、化妆品。(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮还对金黄色葡萄球菌ATCC29213显示出较强的抑制活性，其MIC50值为134.50μM，可用于金黄色葡萄球菌抗菌剂的制备。
最后，(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮对α-葡萄糖苷酶的IC50值为2.45μM，可以应用于治疗糖尿病的药物的制备。
同时，(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的制备方法，操作简单、反应条件温和，无需无氧和高温反应，产率高，可进行工业化大量制备。
具体实施方式
为详细说明技术方案的技术内容、构造特征、所实现目的及效果，以下结合具体实施例详予说明。
实施例1：(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的合成
将(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮(62mg，0.24mmol)、无水1,4-二氧六环(5mL)和三氟化硼乙醚(0.10mL，0.72mmol，3.0N)依次加入25mL圆底烧瓶中，搅拌使其溶解，滴加入2-甲基-3-丁烯-2-醇(0.075mL，0.72mmol，3.0N)，加热至60℃反应0.5h。提升反应瓶，冷却，将反应液倒入适量水中，静置，析出粘稠液，用乙酸乙酯萃取(12mL×3)，合并有机相，饱和食盐水洗涤(10mL×3)，无水硫酸钠干燥，减压蒸除溶剂，得初产物。
以乙酸乙酯和石油醚的混合溶剂为洗脱剂，初产物用中压制备色谱分离纯化，得0.030g暗红色固体，产率为32.0％，mp:153-156℃。该产物的化学名为(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮，简称为化合物1，结构如化学式(Ⅰ)所示：
波谱数据如下：IR(KBr)vmax 638,807,972,984,1083,1132,1289,1376,1447,1596,1626,2856,2925,2968,3415cm-1；1H NMR(500MHz,丙酮-d6)δ1.34(s,6H,2CH3-),1.44(s,6H,2CH3-),3.05(dd,2H,J＝7.0,15.0Hz,-CH2-),3.18(dd,2H,J＝7.0,15.0Hz,-CH2-),5.01(t,2H,J＝7.0Hz,H-2”,H-2”’),6.29(dd,1H,J＝2.4,8.8Hz,H-5’),6.34(d,1H,J＝2.4Hz,H-3’),7.00(d,1H,J＝8.8Hz,H-6’),7.31(s,3H,HO-3,HO-4,HO-5),8.50(s,1H,HO-4’),12.84(s,1H,HO-2’)；13C NMR(125MHz,丙酮-d6)δ17.4,20.4,22.1,25.7,25.8,26.6,103.0,107.6,108.3,116.1,117.8,119.8,123.2,124.1(C-2,C-6),131.1,134.1,134.9,137.2,142.9,165.8,166.5,204.1。
实施例2-5均采用(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮为对比例，以说明本发明(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的特殊生物活性及特有的有益效果，(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮的结构如化学式(Ⅱ)所示：
实施例2：(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的抗肿瘤活性研究
(1)MTS法检测细胞活性原理
MTS为一种全新的MTT类似物，是一种黄颜色的染料。活细胞线粒体中琥珀酸脱氢酶能够代谢还原MTS，生成可溶性的甲臜(Formazan)化合物，甲臜的含量可以用酶标仪在490nm处进行测定。在通常情况下，甲臜生成量与活细胞数成正比，因此可根据光密度OD值推测出活细胞的数目。
(2)实验方法
①接种细胞：用含10％胎牛血清的培养液(DMEM或者RMPI1640)配成单个细胞悬液，以每孔3000-15000个细胞接种到96孔板，每孔体积100μl，贴壁细胞提前12-24h接种培养。
②加入待测化合物溶液：化合物用DMSO(二甲基亚砜)溶解，化合物以40μM浓度初筛，每孔终体积200μl，每种处理均设3个复孔。
③显色：37℃培养48h后，贴壁细胞弃孔内培养液，每孔加MTS溶液20μl和培养液100μl；悬浮细胞弃100μl培养上清液，每孔加20μl的MTS溶液；设3个空白复孔(20μl的MTS溶液和100μl的培养液的混合液)，继续孵育2-4h，使反应充分进行后测定光吸收值。
④比色：选择492nm波长，多功能酶标仪(MULTISKAN FC)读取各孔光吸收值，记录结果，数据处理后以化合物编号为横坐标，细胞抑制百分比为纵坐标绘制肿瘤细胞的抑制图。
⑤检测内容包括5种人类肿瘤细胞和2种人类正常细胞。它们分别是白血病HL-60、肺癌A-549、肝癌SMMC-7721、乳腺癌MCF-7、结肠癌SW480、正常肝细胞L02、正常肺上皮细胞BEAS-2B。
⑥对于抑制百分比超过50％的细胞，再测定化合物对该细胞的IC50值(指抑制一半细胞、酶和微生物等需达到的化合物的浓度)。每次实验均设顺铂(DDP)和紫杉醇(Taxol)两个阳性化合物，以浓度为横坐标，细胞存活百分比为纵坐标绘制细胞生长曲线，按Reed&Muench法[Ref:Reed,L.J.；Muench,H.A simple method of estimating fifty percentendpoints[J].Am.J.Hyg.1938,27,493-497.]计算化合物的IC50值。
按上述技术方案的实验方法，以顺铂(DDP)和紫杉醇(Taxol)为阳性对照化合物，取少量的样品溶解于DMSO中，将其配成40μM溶液，然后对上述5种人类癌细胞和2种人类正常细胞进行抑制活性检测，结果如表1-3所示。
表1浓度为40μM的对比例和化合物1对5种常见癌细胞的抑制活性
表2浓度为40μM的化合物1对肝和肺的正常细胞的抑制活性
表3化合物1对相关癌细胞的IC50值
从表1可以看出：对比例对5株常见人类肿瘤细胞的抑制活性都很低，其抑制百分比为5.16％-22.63％。从表1和3可以看出：化合物1对白血病HL-60、肝癌SMMC-7721、乳腺癌MCF-7和结肠癌SW480都显示出明显的抑制活性，其IC50值为21.63-35.56μM。
从表2可以看出：40μM的化合物1对人类的肝和肺的正常细胞的毒性都较小，其对正常肝细胞L02和正常肺上皮细胞BEAS-2B的抑制百分比分别为33.05％和12.13％。
可见，相对于对比例，其修饰产物化合物1的抗肿瘤活性明显增强。
实施例3：(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的DPPH自由基清除实验实验方法：将待测样品与DPPH(全称为1,1-二苯基-2-三硝基苯肼，终浓度为100μM)混合反应，设定3个重复孔，同时设置不含样品的空白对照孔和Trolox(水溶性维生素E)阳性对照孔，30℃，1h，酶标仪测定OD(optical density，光密度)值，检测波长为515nm，计算得到抗氧化百分比。IC50也是按Reed&Muench法计算。
抗氧化百分比(％)＝(1-实验孔OD515nm/空白孔OD515nm)×100％
按上述技术方案的实验方法，以Trolox为阳性对照化合物，进行DPPH自由基清除实验，结果如表4和表5所示。
表4对比例和化合物1的DPPH自由基清除活性
注：“-”表示没有检测，下同。
将表4中Trolox、对比例和化合物1的抗氧化百分比按Reed&Muench法计算，求出相应的IC50值并列于表5。在表4中，浓度为100μM的对比例的抗氧化百分比为57.64％，故未进一步测其IC50值。
表5化合物1的抗氧化IC50值
从表4和5可以得出：对比例显示出中等的抗氧化活性，而化合物1显示出较强的抗氧化活性；Trolox和化合物1的抗氧化IC50值分别为4.08μg/mL和11.57μg/mL，前者的抗氧化活性强于后者。总之，对比例经过结构修饰后，得到的化合物1的抗氧化活性显著增强。
抗氧化是指抗氧化自由基。科学研究表明，癌症、衰老或其它疾病大都与过量自由基的产生有关。抗氧化作用可以有效克服自由基所带来的危害，所以抗氧化剂可以被开发成抗肿瘤药、保健品和化妆品等。因此，化合物1有望被开发成抗肿瘤药、保健品和化妆品等。
实施例4：(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的抗菌活性实验实验方法：取96孔培养板，将待测样品进行稀释，各孔加入细菌菌液，终浓度为5×105CFU/mL，37℃培养24h，用酶标仪测定625nm下的OD值。检测的细菌包括大肠埃希氏菌(Escherichia coli)ATCC25922、金黄色葡萄球菌金黄亚种(Staphylococcusaureus subsp.aureus)ATCC29213、肠沙门氏菌肠亚种(Salmonella entericasubsp.enterica)ATCC14028、铜绿假单胞菌(Pseudomonas aeruginosa)ATCC27853。实验同时设置培养基空白对照、细菌对照以及青霉素G钠、头孢他啶阳性药对照。
按上述技术方案的实验方法，以青霉素G钠和头孢他啶为阳性对照化合物，进行抗菌活性实验，实验结果如表6-8所示。
表6对比例和化合物1对4种细菌的抑制活性
由表6可得出：浓度为200μM时，对比例对上述4种细菌均未显示出抑制活性，而化合物1对金黄色葡萄球菌ATCC29213显示出强的抑制活性，其抑制百分比为95.94％。
化合物1对金黄色葡萄球菌ATCC29213的抑制活性被进一步检测并被列于表7。将表7的抑制百分比按Reed&Muench法计算，求出相应的MIC50值并列于表8。
表7化合物1对金黄色葡萄球菌ATCC29213的抑制活性
表8化合物1对金黄色葡萄球菌ATCC29213的MIC50值
由表8可得出：化合物1对金黄色葡萄球菌ATCC29213显示出较好地抑制活性，其MIC50值为134.50μM。
实施例5：(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮抑制α-葡萄糖苷酶活性的实验实验方法：将样品(终浓度为50μM)与酶溶液(终浓度为0.025U/ml)、缓冲液、底物(终浓度为1mM)依次加入96孔酶标板，充分混匀，设定2个重复孔。同时设置不含药物的空白对照和槲皮素(终浓度为10μM)阳性对照。37℃孵育50min，酶标仪测定405nm处的OD值，计算得出α-葡萄糖苷酶活性的抑制百分比。化合物的IC50值也是按Reed&Muench法计算。
抑制百分比(％)＝(1-实验孔OD405nm/空白孔OD405nm)×100％
按上述技术方案的实验方法，以槲皮素为阳性对照化合物，进行抑制α-葡萄糖苷酶活性的实验，实验结果如表9和10所示。先测定浓度为50μM的化合物对α-葡萄糖苷酶的抑制活性。如果化合物的抑制百分比超过50％，再测其IC50值。
表9对比例和化合物1对α-葡萄糖苷酶的抑制活性
从表9可以得出：浓度为50μM时，对比例和化合物1对α-葡萄糖苷酶的抑制百分比分别为37.69％和98.53％。因此，化合物1对α-葡萄糖苷酶的IC50值被检测，并列于表10。
表10化合物1对α-葡萄糖苷酶的IC50值
从表10可以得出：槲皮素和化合物1对α-葡萄糖苷酶的IC50值分别为7.40μM和2.45μM。因此，化合物1显示出很强地抑制α-葡萄糖苷酶的活性。α-葡萄糖苷酶抑制剂通过竞争性抑制小肠上皮绒毛膜上的糖苷酶的作用来减少糖类的降解，延缓糖类的消化和吸收，从而有效地降低糖尿病人餐后高血糖的风险，达到控制血糖的目的。可见，化合物1有望被开发成治疗糖尿病的药物。
综上所述，本发明所合成的化合物(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮为一种新的二苯甲酮类化合物，未见文献或者专利对其合成及生物活性进行报道。该化合物对人类的肝和肺的正常细胞的毒性较小，具有明显的抗肿瘤活性，可用于制备抗肿瘤药物；具有较强的抗氧化活性，可应用于抗氧化的药物、保健品、化妆品的制备。同时，(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮对金黄色葡萄球菌ATCC29213显示出较强的抑制活性，其MIC50值为134.50μM，可用于金黄色葡萄球菌抗菌剂的制备。最后，(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮对α-葡萄糖苷酶显示出强的抑制活性，其IC50值为2.45μM，可以应用于治疗糖尿病的药物的制备。
需要说明的是，在本文中，诸如第一和第二等之类的关系术语仅仅用来将一个实体或者操作与另一个实体或操作区分开来，而不一定要求或者暗示这些实体或操作之间存在任何这种实际的关系或者顺序。而且，术语“包括”、“包含”或者其任何其他变体意在涵盖非排他性的包含，从而使得包括一系列要素的过程、方法、物品或者终端设备不仅包括那些要素，而且还包括没有明确列出的其他要素，或者是还包括为这种过程、方法、物品或者终端设备所固有的要素。在没有更多限制的情况下，由语句“包括……”或“包含……”限定的要素，并不排除在包括所述要素的过程、方法、物品或者终端设备中还存在另外的要素。此外，在本文中，“大于”、“小于”、“超过”等理解为不包括本数；“以上”、“以下”、“以内”等理解为包括本数。
尽管已经对上述各实施例进行了描述，但本领域内的技术人员一旦得知了基本创造性概念，则可对这些实施例做出另外的变更和修改，所以以上所述仅为本发明的实施例，并非因此限制本发明的专利保护范围，凡是利用本发明说明书内容所作的等效结构或等效流程变换，或直接或间接运用在其他相关的技术领域，均同理包括在本发明的专利保护范围之内。
Claims (9)
1.一种新的二苯甲酮类化合物，(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮，其结构如化学式(Ⅰ)所示：
2.一种新的二苯甲酮类化合物，(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的制备方法,其特征在于，包括：(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮在无水1,4-二氧六环、三氟化硼乙醚和2-甲基-3-丁烯-2-醇的体系中反应，生成(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮的过程。
3.根据权利要求2所述的制备方法，其特征在于，所述(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮、三氟化硼乙醚与2-甲基-3-丁烯-2-醇的摩尔比为1：3：3。
4.根据权利要求2所述的制备方法，其特征在于，包括以下步骤：
将(2,4-二羟基苯基)(3,4,5-三羟基苯基)甲酮、无水1,4-二氧六环和三氟化硼乙醚依次加入反应容器中，搅拌使其溶解后，滴加2-甲基-3-丁烯-2-醇，50-70℃反应20-40min；反应完毕，将反应液倒入水中，析出粘稠物，萃取得到初产物；
初产物用中压制备色谱分离纯化，得到(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮。
5.(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在制备抗肿瘤药物方面的应用，所述肿瘤包括白血病HL-60、肝癌SMMC-7721、乳腺癌MCF-7和结肠癌SW480。
6.(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在抗氧化药物方面的应用。
7.(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在抑制金黄色葡萄球菌ATCC29213活性药物方面的应用。
8.(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在抑制α-葡萄糖苷酶活性药物方面的应用。
9.(2,4-二羟基苯基)(2,6-二(3-甲基-2-丁烯基)-3,4,5-三羟基苯基)甲酮在制备治疗糖尿病的药物方面的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010843889.5A CN111943830B (zh) | 2020-08-20 | 2020-08-20 | 一种新的二苯甲酮类化合物及其制备方法和应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010843889.5A CN111943830B (zh) | 2020-08-20 | 2020-08-20 | 一种新的二苯甲酮类化合物及其制备方法和应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111943830A CN111943830A (zh) | 2020-11-17 |
| CN111943830B true CN111943830B (zh) | 2023-01-31 |
Family
ID=73358992
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010843889.5A Active CN111943830B (zh) | 2020-08-20 | 2020-08-20 | 一种新的二苯甲酮类化合物及其制备方法和应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111943830B (zh) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101602657A (zh) * | 2009-07-16 | 2009-12-16 | 李青山 | 卤代羟基芳酮类化合物及其制备方法和用途 |
| CN107586721B (zh) * | 2016-07-07 | 2020-09-08 | 中国科学院海洋研究所 | 一种具有抗氧化活性的二苯甲酮类化合物及其制备方法和应用 |
| CN107365336A (zh) * | 2017-07-26 | 2017-11-21 | 华南农业大学 | 一种从番石榴叶中提取的新化合物、制备方法及其用途 |
| CN111285767A (zh) * | 2020-02-19 | 2020-06-16 | 黑龙江中医药大学 | 一种二苯甲酮类化合物及其应用 |
| CN111393277B (zh) * | 2020-03-15 | 2023-01-03 | 山西医科大学 | 4-丁基多羟基二苯甲酮类化合物衍生物及其应用 |
| CN111333495B (zh) * | 2020-04-20 | 2023-01-31 | 莆田学院 | (4-甲氧基-3-羟基苯基)(3,5-二甲基-2-羟基苯基)甲酮及制备方法和应用 |
-
2020
- 2020-08-20 CN CN202010843889.5A patent/CN111943830B/zh active Active
Non-Patent Citations (3)
| Title |
|---|
| 3种顺铂注射制剂的稳定性研究;肖红军等;《广东药学院学报》;20050225(第01期);第32-33页 * |
| 紫杉醇在水环境中的降解动力学研究;于湘莉等;《上海交通大学学报(农业科学版)》;20091015(第05期);第520-523页 * |
| 顺铂稳定性实验观察;李斌等;《甘肃医药》;20101031(第05期);第578-580页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111943830A (zh) | 2020-11-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107759558B (zh) | 一种三氟甲基取代的氧杂蒽酮类化合物及其制备方法和应用 | |
| Rosa et al. | Chalcones and flavanones bearing hydroxyl and/or methoxyl groups: Synthesis and biological assessments | |
| CN109705017B (zh) | 一种查尔酮吲哚衍生物在制备抗肿瘤药物中的应用 | |
| CN113072611A (zh) | 一种甘草次酸修饰的多吡啶钌配合物及其制备方法和应用 | |
| CN114031592A (zh) | 查尔酮衍生物及其制备和在制备抗肿瘤药物或功能食品中的应用 | |
| Era et al. | Production of ellagitannin hexahydroxydiphenoyl ester by spontaneous reduction of dehydrohexa-hydroxydiphenoyl ester | |
| CN111943830B (zh) | 一种新的二苯甲酮类化合物及其制备方法和应用 | |
| Hasan et al. | Synthesis of 6-aminomethyl derivatives of benzopyran-4-one with dual biological properties: anti-inflammatory-analgesic and antimicrobial | |
| CN113387915A (zh) | 一种桉烷型倍半萜内酯类tbb衍生物及其制备方法、用途 | |
| Zhu et al. | Preparation and activity evaluation of chrysin-β-D-galactopyranoside | |
| Chen et al. | Seven new 2-(2-phenethyl) chromone derivatives from agarwood of Aquilaria walla | |
| CN111333495B (zh) | (4-甲氧基-3-羟基苯基)(3,5-二甲基-2-羟基苯基)甲酮及制备方法和应用 | |
| Bjorøy et al. | Structural properties of anthocyanins: Rearrangement of C-glycosyl-3-deoxyanthocyanidins in acidic aqueous solutions | |
| YOSHIDA et al. | Tannins and Related Polyphenols of Euphorbiaceous Plants. V.: Euphorbin C, an Equilibrated Dimeric Dehydroellagitannin Having a New Tetrameric Galloyl Group | |
| CN110981927B (zh) | 三乙酰吡喃糖并二氢吡咯的衍生化反应及衍生产物的应用 | |
| CN100567243C (zh) | 查耳酮衍生物及其用途 | |
| CN114933582A (zh) | 基于对h2o2响应的茶叶提取物egcg前药及其制备方法和应用 | |
| CN104672191B (zh) | 胡枝子酚e1类化合物及制备方法和应用 | |
| CN111892486B (zh) | 一种羟基取代的二苯甲酮类化合物及其制备方法和应用 | |
| CN112679443B (zh) | 一种果糖嗪的制备方法及用途 | |
| CN110183320B (zh) | 一类多烯二酮类抗肿瘤化合物 | |
| Xie et al. | A new cyclodemethylanhydroicaritin from extraction of Epimedium wushanense and evaluation of its biological activities | |
| Sibat | Synthesis and antibacterial activity of 4'-methoxy-5, 7-dimethoxyflavanone & 2, 4-(4-butylphenyl)-5, 7-dimethoxychroman-4-one | |
| KR20130039916A (ko) | 벤조히드록시메톡시칼콘을 유효성분으로 포함하는 항암제 조성물 | |
| de la Torre-Rubio et al. | Carbohydrate effect of novel arene Ru (II) phenanthroline-glycoconjugates on metastatic biological processes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |