异紫堇碱及其类似物抗癌活性研究.docVIP

异紫堇碱及其类似物抗癌活性研究 　　[摘要]采用天然产物化学研究手段，从秃疮花和云南地不容中分离得到部分异紫堇碱类生物碱，并对异紫堇碱进行化学结构修饰得到异紫堇碱类似物，采用MTT法考察了异紫堇碱类似物对3种人癌细胞株的细胞生长抑制活性。结果表明异紫堇碱及其类似物均具有一定的抗癌活性，结合异紫堇碱及其类似物的单晶衍射结构与EGFR分子对接模拟，从立体化学结构、化合物不同取代基位置以及芳香环电子云密度等角度探讨了该类化合物具有抗癌活性的构效关系。 　　[关键词]阿朴啡类生物碱； 抗癌活性； 构效关系； 异紫堇碱 　　Research on anticancer activity of isocorydine and its derivatives 　　YAN Qian1，2， LI Ruxia1，3， XIN Aiyi1，2， LIU Junxi1*， LI Wenguang2， DI Duolong1 　　（1Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of 　　Gansu Province， Lanzhou Insititute of Chemical Physics， Chinese Academy of Science， Lanzhou 730000， China； 　　2 School of Basic Medical Sciences， Lanzhou University， Lanzhou 730000， China； 　　3 University of Chinese Academy of Sciences， Beijing 100049， China） 　　[Abstract]Isocorydine and its analogs were extracted from Dicranostigma leptopodum and Stephania yunnanensis through the method of natural products chemistry Its derivatives were prepared by chemical structure modifications from isocorydine MTT method was used to study the inhibitory effect of those compounds on the growth of HepG2， HeLa and MGC803 cancer cell lines in vitro The results showed that isocorydine and its analogs all have the growth inhibition for those cancer cell lines This paper investigated the structureactivity relationship of isocorydine and its derivatives with anticancer activity in the aspect of stereochemical structure， functional groups positions of the compounds and the electron density of aromatic rings based on the single crystal diffraction structure and the molecular docking of EGFR and isocorydine 　　[Key words]aporphine alkaloids； anticancer activity； SAR； isocorydine 　　天然?a物是多种重要疾病治疗药物的关键先导化合物[1]，通过考察天然产物的生物学活性与取代基、官能团之间的构效关系，结合药物结构设计对化合物进行结构修饰，提高其活性是新药开发的一条非常重要的途径。阿朴啡类生物碱（aporphine alkaloids）分布于20个科100多属的植物中[2]，是异喹啉类生物碱的一种，为一类重要的植物次生代谢产物。该类生物碱具有多种药理活性，包括抗氧化、抗惊厥、抗痉挛、抗血小板凝聚、细胞毒性等，其中最能引起广泛关注的是此类生物碱具有良好的抗肿瘤活性。 　　异紫堇碱（isocorydine，音译名：异可利定，国药准字属解痉镇痛药）是典型的天然