CN113024527A - Compound derived from Zhejiang ophiopogon root, application and pharmaceutical composition thereof - Google Patents
Compound derived from Zhejiang ophiopogon root, application and pharmaceutical composition thereof Download PDFInfo
- Publication number
- CN113024527A CN113024527A CN202110313549.6A CN202110313549A CN113024527A CN 113024527 A CN113024527 A CN 113024527A CN 202110313549 A CN202110313549 A CN 202110313549A CN 113024527 A CN113024527 A CN 113024527A
- Authority
- CN
- China
- Prior art keywords
- compound
- dichloromethane
- cancer
- medicament
- treatment
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 71
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 229930195210 Ophiopogon Natural products 0.000 title abstract description 8
- 244000248557 Ophiopogon japonicus Species 0.000 title abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 10
- 238000000926 separation method Methods 0.000 claims description 9
- 238000010898 silica gel chromatography Methods 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- 239000003208 petroleum Substances 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 208000032839 leukemia Diseases 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 239000002037 dichloromethane fraction Substances 0.000 claims description 4
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 238000010828 elution Methods 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 230000002441 reversible effect Effects 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 240000002948 Ophiopogon intermedius Species 0.000 claims 1
- 201000005787 hematologic cancer Diseases 0.000 claims 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 4
- -1 flavonoid compound Chemical class 0.000 description 12
- 230000001093 anti-cancer Effects 0.000 description 9
- 239000000463 material Substances 0.000 description 8
- 229930014626 natural product Natural products 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 241001448424 Ophiopogon Species 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 229940041181 antineoplastic drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010011224 Cough Diseases 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241001448421 Ophiopogon jaburan Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 229930003935 flavonoid Natural products 0.000 description 3
- 235000017173 flavonoids Nutrition 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical compound C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 229930190714 ophiopogonone Natural products 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- 208000031971 Yin Deficiency Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 208000017574 dry cough Diseases 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 238000001052 heteronuclear multiple bond coherence spectrum Methods 0.000 description 2
- 238000000990 heteronuclear single quantum coherence spectrum Methods 0.000 description 2
- 150000002611 lead compounds Chemical class 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 230000035922 thirst Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- RWXIFXNRCLMQCD-JBVRGBGGSA-N (20S)-ginsenoside Rg3 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RWXIFXNRCLMQCD-JBVRGBGGSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 238000001026 1H--1H correlation spectroscopy Methods 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- XIRZPICFRDZXPF-UHFFFAOYSA-N Ginsenoside Rg3 Natural products CC(C)=CCCC(C)(O)C1CCC(C2(CC(O)C3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O XIRZPICFRDZXPF-UHFFFAOYSA-N 0.000 description 1
- 208000000616 Hemoptysis Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 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
- 241000234280 Liliaceae Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 244000184734 Pyrus japonica Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 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
- 241001116500 Taxus Species 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000004729 acetoacetic acid derivatives Chemical class 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- GOMNOOKGLZYEJT-UHFFFAOYSA-N isoflavone Chemical group C=1OC2=CC=CC=C2C(=O)C=1C1=CC=CC=C1 GOMNOOKGLZYEJT-UHFFFAOYSA-N 0.000 description 1
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 1
- 150000002515 isoflavone derivatives Chemical class 0.000 description 1
- 235000008696 isoflavones Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229940037627 magnesium lauryl sulfate Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 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
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Technical Field
The invention relates to a compound and medical application thereof, and also relates to a pharmaceutical composition containing the compound.
Background
Obtaining anti-tumor drugs from natural products is a popular field for the development of tumor drugs at home and abroad at present. The american National Cancer Institute (NCI) commissioned a phytologist of the american ministry of agriculture (USDA) in 1960 to provide 1000 plants annually to the national cancer chemotherapy service center (CCNSC) for anti-cancer drug screening. Over the years of efforts, the anticancer of natural products has also made great progress, and many natural small molecules have been successfully put on the market and become the star therapeutic drugs in the corresponding fields, such as taxus, camptothecin, vincristine, ginsenoside Rg3, and the like. As a natural product, China has huge natural product resources and also has a history of developing and using natural products which are far away, so that a plurality of scientists in China are always dedicated to the development of natural anti-tumor drugs. The traditional Chinese medicine has unique advantages in the aspects of resisting and preventing cancers, reducing adverse reactions and the like, and is a treasure house for researching and developing novel anti-tumor medicines.
In order to find more desirable anti-cancer compounds, scientists have not stopped the step of finding compounds of plant origin with anti-cancer activity.
Thunberg lilyturf root (Ophiopogon japonica (Thunb.) Ker-Gawl), is a perennial evergreen herb of the genus Ophiopogon of the family Liliaceae. The fibrous root is thicker, and the top or middle part of the root is often expanded to form spindle-shaped small fleshy blocks, which are Chinese medicinal materials. The traditional Chinese medicine believes that the Zhejiang dwarf lilyturf tuber is slightly bitter and cold. It enters heart, lung and stomach meridians. Has the effects of nourishing yin, promoting the production of body fluid, moistening lung and clearing away heart-fire. Can be used for treating lung dryness, dry cough, consumptive disease, cough, thirst due to body fluid consumption, vexation, insomnia, internal heat, diabetes, constipation due to intestinal dryness, and pharyngeal diphtheria. Simultaneously, the medicine is used for treating little body fluid, thirst, dry cough and hemoptysis caused by lung-stomach yin deficiency; palpitation due to heart yin deficiency and fluid impairment due to heat in the late stage of fever.
In the experiment of screening the anti-tumor compound, the inventor tries to screen the lead compound with anti-tumor activity from the natural compound derived from the thunberg dwarf lilyturf tuber, thereby providing a new choice for the research, development and preparation of novel anti-cancer drugs.
Disclosure of Invention
The inventor of the invention carries out intensive research on chemical components of the traditional Chinese medicine Zhe dwarf lilyturf tuber, and separates out a novel flavonoid compound of the dwarf lilyturf tuber, the structural formula of which is shown as the formula (I):
depending on the skeletal classification of the compound, the compound should belong to the homoisoflavonoid class of compounds. Homoisoflavonoids are a special class of flavonoids, which have a parent structure with one more carbon atom than isoflavones, are found in nature rarely and are present in only a few plants.
The homoisoflavone of the invention is specifically methyl homoisoflavone, also called Ophiopogonone (Ophiopogonone) compound, and has two more carbon atoms compared with the conventional isoflavone skeleton.
The chemical formula of the compound shown in the formula (I) according to the general systematic numbering of the flavonoids in natural products is as follows:
according to the inventor's examination, the compound with methylation at the 6-position of the skeleton and methoxyl at the 2' -position, and the 4 'and 3' ring-forming has not been reported from the natural product world, and the compound is not synthesized, and is determined to be the first discovered compound.
The content of the compound of the invention in natural medicinal materials is lower through the measurement of the dry medicinal materials and the finally obtained compound magnitude, according to the calculation of the inventor, the content in the dry medicinal materials is about 1.2ppm, and the related activity of the natural medicinal materials cannot be directly related to the activity of the compound.
Furthermore, the novel structural compound described in the formula (I) shows obvious anticancer activity in an anticancer activity test. The compounds from Thunberg lilyturf root, which have anticancer activity potential reported so far, have larger structural difference with the compounds of the formula (I) of the invention, and provide a new choice for the research, development and preparation of novel anticancer drugs.
Specifically, the invention provides the following technical scheme:
the invention provides a compound, which has a structure shown in a formula (I):
in the present invention, unless otherwise specified, chemical elements generally include the concept of chemically identical isotopes, such as the expression "hydrogen" and also the concept of chemically identical "deuterium" and "tritium", and carbon (C) includes12C、13C, etc., will not be described in detail. That is, the compound of the present invention includes a case where the element is replaced with an isotope.
The compound or the physiologically acceptable salt thereof can be applied to the preparation of a medicament for treating cancer because the compound or the physiologically acceptable salt thereof shows anticancer activity (see the specific embodiment), and the medicament for treating cancer is preferably a medicament for treating leukemia, liver cancer, breast cancer and colon cancer, but is not limited to the anticancer medicaments, and is preferably a medicament for treating leukemia.
In addition, the invention also provides a pharmaceutical composition which comprises the compound shown in the formula (I) and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be used in combination with pharmaceutically acceptable adjuvants when the compound of the present invention is formulated, and examples of the adjuvants include solvents (e.g., water, ethanol, propylene glycol, oil for injection, etc.) which are conventional in the pharmaceutical field, diluents (e.g., starch, sugar powder, dextrin, lactose, pregelatinized starch, microcrystalline fiber, inorganic calcium salts (e.g., calcium sulfate, calcium hydrogen phosphate, calcium carbonate for pharmaceutical use, etc.), mannitol, etc., vegetable oils, polyethylene glycol, etc.), binders (e.g., water, ethanol, starch slurry, sodium carboxymethylcellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose, etc.), disintegrants (e.g., dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crospovidone, croscarmellose sodium, etc.), lubricants (e.g., magnesium stearate, sodium lauryl sulfate, lauryl sulfate, Aerosil, talc, hydrogenated vegetable oil, polyethylene glycol, magnesium lauryl sulfate, etc.), absorption enhancer (such as surfactant, Azone, EDTA, salicylic acid, amino acid ethylamine derivatives, acetoacetates, β -dicarboxylate, aromatic acidic compound, fatty acid, etc.), preservative (such as benzoic acid, hydroxypropyl butyl ester, hydroxypropyl methyl ester, phenol, m-cresol, etc.), taste corrigent (such as sucrose, steviosin, etc.), etc. But is not limited thereto.
The pharmaceutical composition of the present invention can be used in various dosage forms, i.e., can be administered by conventional preparation methods, such as tablets, capsules, dripping pills, granules, powders, oral films and oral liquids, or injections, ointments, creams, suppositories, and the like, but is not limited thereto. The compound of the present invention is preferably formulated into an oral preparation for the purpose of treatment and convenience.
The compound can be extracted from the root bark of the Zhejiang ophiopogon root traditional Chinese medicinal material. The invention also provides an extraction preparation method, which is characterized by comprising the following steps:
an enrichment step, extracting dry root tuber powder of the thunberg lilyturf root with 80-95% ethanol, dissolving extraction residues in water, and extracting with dichloromethane to obtain dichloromethane fraction;
and a crude separation step, namely performing normal phase silica gel column chromatography on the dichloromethane fraction obtained in the step, and performing gradient elution by adopting a petroleum ether-dichloromethane gradient solvent system, wherein the solvent ratio is changed into petroleum ether: the volume ratio of dichloromethane is changed from 10:1 to 2:1 to obtain corresponding components;
and a fine separation step, namely performing normal phase silica gel column chromatography on the components separated in the fine separation step again, performing gradient by using dichloromethane-methanol, and changing the solvent ratio into dichloromethane: changing methanol from 65:1 to 5:1 in volume ratio, and eluting to obtain corresponding components;
and a purification step, namely performing chromatography on the components separated in the fine separation step on a reverse phase silica gel column chromatography to obtain the target compound.
The invention can of course also be obtained according to fully synthetic or semi-synthetic methods, which can be obtained according to organic synthetic methods well known in the art.
Drawings
FIG. 1 is a drawing of a compound of the present invention1H NMR spectrum;
FIG. 2 is a drawing of a compound of the present invention13C NMR spectrum;
FIG. 3 is a drawing of a compound of the present invention1H-1H COSY spectrogram;
FIG. 4 is a HSQC spectrum of a compound of the present invention;
FIG. 5 is a HMBC spectrum of a compound of the present invention;
FIG. 6 is a NOESY spectrum of a compound of the present invention;
FIG. 7 is a high resolution mass spectrum of a compound of the present invention;
FIG. 8 is an HPLC chromatogram of a compound of the present invention;
FIG. 9 is a UV spectrum of a compound of the present invention.
Detailed Description
The following describes how the compounds of formula (I) of the present invention (also referred to simply as "compounds of the present invention") can be obtained. Also specifically disclosed are specific experimental methods for the anticancer activity of the compounds of formula (I).
The experimental procedures in the following examples are conventional unless otherwise specified. The raw materials and reagent materials used in the following examples are all commercially available products unless otherwise specified.
Obtaining a compound of formula (I):
the extraction and separation process of the compound of the invention is as follows:
the Zhejiang ophiopogon root is purchased from Cixi Zhejiang, and the product package is provided with a geographical sign registration certificate of agricultural products and is morphologically identified as Zhejiang ophiopogon root.
Extracting 20kg of dried root tuber powder of the medicinal materials with 95% ethanol at room temperature for 3 times, each time for 4 hr. The solvent was removed by concentration under reduced pressure, and the residue (1960 g) was dissolved in water and separated by extraction with petroleum ether (3X 5L), methylene chloride (3X 5L) and ethyl acetate (3X 5L) in that order. The dichloromethane extraction fraction (180g) was separated by silica gel column chromatography eluting with a petroleum ether-dichloromethane (10: 1-1: 1v/v) gradient to give eight fractions (fr.a-fr.h).
② the product (180g) of the extraction part of the dichloromethane in the step (I) is separated by silica gel column chromatography and is eluted by petroleum ether-dichloromethane (10: 1-1: 1v/v) in a gradient way to obtain eight parts (Fr.A-Fr.H).
③ the Fr.C fraction obtained in step (25g) was subjected to silica gel column chromatography and eluted with a gradient (60: 1; 40: 1; 20: 1; 10: 1; 5:1v/v) of dichloromethane-methanol to give six fractions (Fr.1-6).
Fr.2 fraction was prepared by preparative HPLC using YMC Pack ODS-A (50 × 250mm,7um) column, eluting with methanol-water (80:20, v/v), to give the compound represented by formulA (1) of the present invention (25.6mg, tR ═ 10.72 min).
Structural characterization of the compounds of formula (I):
product analysis of the novel compounds obtained in the examples; of the compounds of the invention1The H NMR spectrum is shown in FIG. 1, and the compound of the invention13The C NMR spectrum is shown in FIG. 2, of the compound of the present invention1H-1The HCOSY spectrum is shown in figure 3, the HSQC spectrum of the compound of the invention is shown in figure 4, the HMBC spectrum of the compound of the invention is shown in figure 5, the NOESY spectrum of the compound of the invention is shown in figure 6, the high-resolution mass spectrum of the compound of the invention is shown in figure 7, and the HPLC spectrum of the compound of the invention is shown in figure 8.
In addition, the HPLC detection conditions of FIG. 8 of the present invention are as follows:
a chromatographic column: agilent SB-C18 (4.6X 250mm,5 μm)
Eluent: acetonitrile (A) water (B)
Gradient conditions: 0 → 15 → 23 → 24 → 50 min; 8% → 20% → 28% → 65% → 70% (A)
A detector: 296nm ultraviolet detector
Column temperature: 30 deg.C
Flow rate: 1ml/min
Ultraviolet spectra of the compounds of the invention are shown in FIG. 9
By subjecting it to high resolution MS (M/z 357.0992[ M-H)]-Theoretical value of 357.0980), and the molecular formula of the compound is determined to be C19H18O7。
Analysis of NMR spectra by reference to the following solutionsTo say that: in that1The proton signal of 1 biphenylmethyl group [ delta 1.59(3H, s) ] is shown in the H-NMR spectrum]Proton signal of 1 methoxy group [3.64(3H, s) ]]Proton Signal of 1 methine group [2.48(1H, m)]1 benzene ring methine proton Signal [5.62(1H, s)]1 methylene proton signal with 2 oxygen functional groups [5.58(2H, s)]。1H-1HCOSY spectrum shows that delta 2.22 and delta 2.83 are homocarbon protons, and delta 3.69 and delta 3.85 are homocarbon protons, and the proton signals of 1 group of methylene in the structure are [2.22(1H, m), 2.83(1H, m)]Group 1 methylene proton signals of oxygen-linked functional groups [3.69(1H, m), 3.85(1H, m)]δ 6.10 is related to δ 6.25, and there are 1 groups of benzenoid proton signals in the structure [6.10(1H, d, J ═ 7.9), 6.25(1H, d, J ═ 7.9)]. According to13C-NMR spectroscopy can infer the presence of 1 carbonyl carbon, 1 methyl carbon, 1 methoxy carbon, 1 methylene carbon, 1 methine carbon, 1 methylene carbon attached to an oxygen functionality, 1 methylene carbon attached to a 2 oxygen functionality, 1 penta-substituted phenyl and 1 tetra-substituted phenyl in the structure. Based on comprehensive analysis of HSQC and HMBC, the structure contains a chromone-like fragment and a methoxy methylenedioxybenzyl fragment, and is shown in the following specific structure, wherein the structure is formed by remotely correlating delta 68.22 with delta 2.22 and 2.83, 6.10, remotely correlating delta 0121.98 with delta 12.22, 2.83, 6.10, remotely correlating delta 135.24 with delta 5.58 and 6.10, remotely correlating delta 147.30 with delta 5.58 and 6.25, remotely correlating delta 140.71 with delta 2.22, 2.83, 3.64 and 6.25, and remotely correlating delta 103.08 with delta 1.59, 5.62 and 12.02:
the specific nuclear magnetic data attribution is shown in table 1:
table 1.
Example (b): proliferation inhibitory Effect of the Compound of the present invention on cancer cells
Cytotoxic activity assay methods:
tumor development is the result of loss of regulation of cell function, and abnormalities in growth signaling and cell cycle regulation lead to abnormalities in cell proliferation, ultimately leading to malignant clones. One of the characteristics of cancer cells is abnormal proliferation. Inhibition of cancer cell proliferation is one of the important approaches for cancer treatment and is also a basic requirement for anti-tumor drugs. The new compound is respectively acted on leukemia HL-60, liver cancer SMMC-7721 and breast cancer MCF-7 for 24 hours, and then the absorbance value is measured at the wavelength of 450nm by a CCK-8 method to detect the proliferation inhibition effect of cancer cells.
HL-60, SMMC-7721 and MCF-7 cells at a ratio of 1 × 105Each/mL of the cells was inoculated into a 96-well plate, incubated in a 5% carbon dioxide incubator to the logarithmic phase, and a blank group, a control group and an administration group (the blank group contained only medium and no cells, and each group contained 8 parallel wells) were set, and 40. mu. mol/L of the compound solution was added to each of the administration groups, and the incubation was continued for 24 hours. After 24 hours, 10uL of CCK-8 solution is added into each hole, the culture is continued for 4 hours, the absorbance value OD450nm is detected at 450nm, and the proliferation inhibition effect of the compound on each tumor cell is calculated by using the following formula:
inhibition (%) [ (control OD450 nm-administered group OD450 nm)/((control OD450 nm-blank OD450nm) ] × 100
The specific experimental results are shown in table 2:
TABLE 2
The experiment evaluates the tumor cell proliferation inhibition activity of the ophiopogonone compound, and the result shows that the compound has proliferation inhibition effect on human leukemia HL-60 cells and breast cancer MCF-7 at the concentration of 40 mu mol/L, is an ideal candidate lead compound, and can provide a new research direction for further structure modification and structure-activity relationship research.
The above-mentioned embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements made to the technical solution of the present invention by those skilled in the art without departing from the spirit of the present invention shall fall within the protection scope defined by the claims of the present invention.
Claims (7)
2. use of a compound according to claim 1 and physiologically acceptable salts thereof for the manufacture of a medicament for the treatment of cancer.
3. The use according to claim 2, wherein the medicament for the treatment of cancer is a medicament for the treatment of blood cancer or breast cancer.
4. The use according to claim 2, wherein the medicament for the treatment of cancer is a medicament for the treatment of leukemia.
5. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
6. The composition of claim 5, which is an oral preparation selected from the group consisting of tablets, capsules, dripping pills, granules, powders, oral films and oral liquids; or a non-oral preparation selected from injection, ointment, cream and suppository.
7. A process for the preparation of a compound according to claim 1, comprising the steps of:
an enrichment step, extracting dry root tuber powder of the thunberg dwarf lilyturf tuber with 80-95% ethanol, dissolving concentrated residues of an extracting solution in water, and extracting with dichloromethane to obtain dichloromethane fractions;
and a crude separation step, namely performing normal phase silica gel column chromatography on the dichloromethane fraction obtained in the step, and performing gradient elution by adopting a petroleum ether-dichloromethane gradient solvent system, wherein the solvent ratio is changed into petroleum ether: the volume ratio of dichloromethane is changed from 10:1 to 2:1 to obtain corresponding components;
and a fine separation step, namely performing normal phase silica gel column chromatography on the components separated in the fine separation step again, performing gradient by using dichloromethane-methanol, and changing the solvent ratio into dichloromethane: changing methanol from 65:1 to 5:1 in volume ratio, and eluting to obtain corresponding components;
and a purification step, namely performing chromatography on the components separated in the fine separation step on a reverse phase silica gel column chromatography to obtain the target compound.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110313549.6A CN113024527A (en) | 2021-03-24 | 2021-03-24 | Compound derived from Zhejiang ophiopogon root, application and pharmaceutical composition thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110313549.6A CN113024527A (en) | 2021-03-24 | 2021-03-24 | Compound derived from Zhejiang ophiopogon root, application and pharmaceutical composition thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113024527A true CN113024527A (en) | 2021-06-25 |
Family
ID=76473430
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110313549.6A Pending CN113024527A (en) | 2021-03-24 | 2021-03-24 | Compound derived from Zhejiang ophiopogon root, application and pharmaceutical composition thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113024527A (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102180850A (en) * | 2011-03-26 | 2011-09-14 | 浙江大学 | Dwarf lilyturf tuber medium-high isoflavone compounds, and preparation method and application thereof |
CN102949388A (en) * | 2011-08-29 | 2013-03-06 | 苏州同立医药技术有限公司 | Isoflavones composition and medicine made of same |
KR20200124630A (en) * | 2019-04-24 | 2020-11-03 | 가천대학교 산학협력단 | chromane derivatives, and pharmaceutical composition for preventing or treating neovascular eye disease or cancer containing the same as an active ingredient |
-
2021
- 2021-03-24 CN CN202110313549.6A patent/CN113024527A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102180850A (en) * | 2011-03-26 | 2011-09-14 | 浙江大学 | Dwarf lilyturf tuber medium-high isoflavone compounds, and preparation method and application thereof |
CN102949388A (en) * | 2011-08-29 | 2013-03-06 | 苏州同立医药技术有限公司 | Isoflavones composition and medicine made of same |
KR20200124630A (en) * | 2019-04-24 | 2020-11-03 | 가천대학교 산학협력단 | chromane derivatives, and pharmaceutical composition for preventing or treating neovascular eye disease or cancer containing the same as an active ingredient |
Non-Patent Citations (4)
Title |
---|
CHANG-LING DUAN等: "麦冬须根脂溶性成分研究(英文)", 《JOURNAL OF CHINESE PHARMACEUTICAL SCIENCES》 * |
YONGYI WANG,ET AL.: "Three New Homoisoflavanones from the Ophiopogon japonicus Ker-Gawler (Liliaceae)", 《HELVETICA CHIMICA ACTA》 * |
姜醒 等: "麦冬中具有生物活性的高异黄酮类化学成分研究", 《中国现代中药》 * |
江洪波 等: "天然高异黄酮的研究进展", 《药学学报》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107746397B (en) | Compound Oleracone C and its extraction separation method in purslane | |
CN109897077A (en) | Compound Oleraciamide E and its extraction separation method and application in purslane | |
CN110627861B (en) | Anemarrhena steroid saponin compound and preparation method and application thereof | |
CN106916193B (en) | A method of extracting afzclin from cercis leaf | |
CN110272342A (en) | A kind of naphthoic acid compound and its extraction separation method and purposes in purslane | |
CN108191616B (en) | Monomer component with selective butyrylcholine esterase inhibition effect in bletilla striata and application thereof | |
Stefkó et al. | Phenanthrenes from Juncus atratus with antiproliferative activity | |
CN106008502A (en) | Alkaloid compounds with novel skeletons in purslane and extraction and separation method thereof | |
Xiang et al. | Screening, characterization of trace α-glucosidase inhibitors from the root of Pueraria lobata and evaluation of their hypoglycemic activity | |
Wang et al. | Methyl 2-naphthoates with anti-inflammatory activity from Morinda officinalis | |
CN102180850A (en) | Dwarf lilyturf tuber medium-high isoflavone compounds, and preparation method and application thereof | |
CN109336747A (en) | Oleralignan and its extraction separation method and its application in purslane | |
CN106083556B (en) | Azulene structural compounds and its extraction separation method in purslane | |
CN110028535B (en) | Diterpene glycoside compounds in longtube ground ivy herb and extraction and separation method thereof | |
CN111471053A (en) | Prenylated flavonoid compound sinopodone and preparation method and application thereof | |
CN113024527A (en) | Compound derived from Zhejiang ophiopogon root, application and pharmaceutical composition thereof | |
CN110452248A (en) | A kind of novelty sesquiterpenoid and the preparation method and application thereof | |
CN105949266A (en) | Withana lactide compound, method for extracting same and application of withana lactide compound | |
Zhang et al. | Three New Labdane‐Type Diterpenoids from the Fruits of Amomum villosum and Their Anti‐Inflammatory Activities | |
CN105601693A (en) | Preparation method and antitumor effect of ginsenoside F1 | |
CN113045526A (en) | Thunberg ophiopogon root source compound and application and pharmaceutical composition thereof | |
CN112824383B (en) | Bibenzyl compound and preparation method and application thereof | |
CN109206392B (en) | Coumarin compound and preparation method and application thereof | |
CN111377933B (en) | Alkaloid compound extracted from orychophragmus violaceus seeds as well as extraction method and application thereof | |
CN114605422A (en) | A pair of enantiomer alkaloid dimer compounds, and preparation method and application thereof |
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 | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210625 |