摘要
目的:研究鬼针草的化学成分,以及部分化合物的体外抗胃癌细胞增殖活性。方法:采用硅胶柱色谱、制备薄层色谱、中压色谱分离凝胶柱色谱、中压制备色谱、半制备高效液相色谱及重结晶等方法进行化合物的分离纯化,结合理化性质、紫外光谱、红外光谱、质谱、核磁共振波谱和圆二色谱等方法鉴定所得化合物的结构。采用噻唑蓝法测定部分化合物对人胃癌SGC-7901细胞的体外抑制活性,并通过分子对接技术预测高活性发挥其抗胃癌作用的潜在靶点。结果:从鬼针草石油醚部位分离得到25个化合物,分别鉴定为鬼针草木脂素A(1)、5α,8α-环二氧-22E,24R-麦角甾-6,22-二烯-3β-醇(2)、3β-羟基豆甾-5-烯-7-酮(3)、(20R)-6β-羟基豆甾-4,22-二烯-3-酮(4)、5,22-二烯-7-酮-3β-羟基豆甾烷(5)、(22E,24S)-24-甲基-5α-胆甾-7,22-二烯-3β,5α,6β-三醇(6)、豆甾-5-烯-3β,7α-二醇(7)、豆甾-5,22-二烯-3β,7α-二醇(8)、7β-羟基谷甾醇(9)、豆甾醇(10)、鹰爪花醇(11)、秋英酸(12)、4(15)-桉烯-1β,6α-二醇(13)、clovandio(l 14)、3-吲哚甲醛(15)、6,7-二甲氧基香豆素(16)、3′,4′-二甲氧基槲皮素(17)、8,8′-bis(-dihydroconiferyl)-diferuloylat(e 18)、hydroxydihydrobovolid(e 19)、2-去乙酰基-11β,13-二氢苍耳亭(20)、黑麦草内酯(21)、豨莶酮(22)、(+)-去氢催吐萝芙木醇(23)、单棕榈酸甘油(24)和正十六烷酸(25)。从鬼针草中分离得到化合物1为新化合物,化合物3~9、11~12、18~20、22~23为首次从鬼针草属植物中分离得到,化合物13和14为首次从该植物中分离得到。化合物17和18对SGC-7901细胞具有较好的体外增殖抑制活性,半数抑制浓度(IC50)分别为3.11μmol·L^(-1)和7.22μmol·L^(-1)。分子对接结果显示,二者发挥抗胃癌活性的潜在作用靶点可能为血管内皮细胞生长因子受体2(VEGFR2)和聚腺苷二磷酸核糖聚合酶7(PARP7)。结论:从鬼针草中分离得到1个新化合物,14个属首分化合物及2个种首分化合物,其中化合物17、18具有体外抗胃癌细胞增殖活性,潜在靶点可能为VEGFR2和PARP7。
Objective:To study the chemical constituents of Bidens pilosa and the in vitro antiproliferative activity of some compounds against gastric cancer cells.Methods:The chemical constituents were isolated and purified by methods such as silica gel column chromatography,preparative thin layer chromatography,medium pressure preparation chromatography,semipreparative high performance liquid chromatography(HPLC)and recrystallization,their structures were identified on the basis of physicochemical properties,spectral data and circular dichroism spectra.Thiazole blue(MTT)assay was used to determine the in vitro inhibitory activityies of some isolated compounds against human gastric cancer SGC-7901 cells,and molecular docking was used to predict their potential targets.Results:Twenty-five compounds were isolated from the petroleum ether fraction of B.pilosa and identified as bidpillignan A(1),5α,8α-epidioxy-(22E,24R)-ergosta-6,22-diene-3β-ol(2),3β-hydroxysitost-5-en-7-one(3),(20R)-6β-hydroxystigmasta-4,22-dien-3-one(4),3β-hydroxylstigmasta-5,22-dien-7-one(5),(22E,24S)-24-methyl-5α-choleata-7,22-diene-3β,5α,6β-triol(6),stigamast-5-ene-3β,7α-diol(7),stigmast-5,22-diene-3β,7α-diol(8),7β-hydroxysitosterol(9),stigmasterol(10),artabotrol(11),cosmosoic acid(12),ent-4(15)-eudesmene-1β,6α-diol(13),clovandiol(14),1H-indole-3-carboxaldehyde(15),6,7-dimethoxycoumarin(16),3',4'-dimethoxyquercetin(17),8,8'-bis-(dihydroconiferyl)-diferuloylate(18),hydroxydihydrobovolide(19),2-deacetyl-11β,13-dihydroxyxanthinin(20),loliolide(21),pubescone(22),(+)-dehydrovomifolio(l 23),2,3-dihydroxypropyl palmitate(24)and n-hexadecane acid(25).Among them,compound 1 was a new compound,compounds 3-9,11-12,18-20,22-23 were first isolated from Bidens genus plants,and compounds 13 and 14 were isolated from this plant for the first time.Compounds 17 and 18 showed good in vitro proliferation inhibitory activities against SGC-7901 cells with the half inhibitory concentrations(IC50)of 3.11,7.22μmol·L^(-1),respectively.Molecular docking results showed that the potential targets of the two exerting anti-gastric cancer activity might be vascular endothelial growth factor receptor 2(VEGFR2)and poly(adenosine diphosphate-ribose)polymerase 7(PARP7).Conclusion:One new compound,14 genus first compounds,and 2 species first compounds were isolated from B.pilosa,among which compounds 17 and 18 processed anti-gastric cancer cell proliferation activity in vitro,and the targets may be VEGFR2 and PARP7.
作者
韩玉
刘畅
刘娇
张涛
邹忠梅
HAN Yu;LIU Chang;LIU Jiao;ZHANG Tao;ZOU Zhongmei(Shenyang Pharmaceutical University,Shenyang 110016,China;Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union College,Beijing 100193,China;Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《中国实验方剂学杂志》
北大核心
2025年第2期154-164,共11页
Chinese Journal of Experimental Traditional Medical Formulae
基金
中国医学科学院医学与健康科技创新工程项目(2022-I2M-1-017)
国家“重大新药创制”科技重大专项(2019ZX09735002)。
关键词
鬼针草
化学成分
分离鉴定
胃癌
分子对接
细胞增殖活性
作用靶点
Bidens pilosa
chemical constituents
isolation and identification
gastric cancer
molecular docking
cell proliferative activity
targets
