基于当归内酯骨架的化合物设计以及体外抗癌活性研究  

Design of compound based on angelicolactone skeleton and research of anticancer activity in vitro

作　　者：方华迎 黄维[1] 詹固 FANG Hua-ying;HUANG Wei;ZHAN Gu(State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan)

机构地区：[1]西南特色中药资源国家重点实验室成都中医药大学,四川成都611137

出　　处：《中药与临床》2023年第2期47-50,共4页Pharmacy and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(22001024)。

摘　　要：目的:以中药当归作为切入点,基于药物活性骨架拼合原理,重点围绕当归内酯骨架展开其类似物的发现、设计、制备以及活性筛选等工作,以期发现一些抗癌活性较好的先导化合物骨架,丰富化合物的分子库,为日后的药物研究提供一定的思路和方法。方法:通过金属银催化烯酰胺环化异构化形成氮杂二烯中间体,随后与腈亚胺发生1,3-偶极环加成反应,生成当归内酯衍生的螺环吡唑啉类似物。对合成的化合物进行体外抗癌活性评价,用MTT法测定了化合物对多种肿瘤细胞株的抑制作用及细胞存活率。结果:成功合成了当归内酯衍生的螺环吡唑啉类似物3a-3f,通过^(1)H-NMR、^(13)C-NMR以及MS-ESI对化合物结构进行了表征;MTT法对合成的化合物进行了体外抗癌活性的评价,实验结果表明3c对HCT116和RKO具有显著的抑制作用,3d对MDA-MB-231具有显著的抑制作用。结论:制备当归内酯衍生的螺环吡唑啉类似物具有潜在抗癌活性。Objective:Angelica sinensis as the starting point,based on the combination principles of drug active skeleton,the discovery,design,preparation,and activity screening of analogues are mainly carried out around the skeleton of angelicalactone,in order to discover the skeleton of some lead compounds with good anticancer activity,enrich the molecular library of compounds,and provide certain ideas and methods for future drug research.Method:The angelicolactone-derived spiropyrazoline analogizes were formed by the cycloisomerization of enamide catalyzed by silver metal to form an azadiene intermediate,followed by 1,3-dipole cycloaddition reaction with nitrile imines.The anticancer activity of the synthesized compounds was evaluated in vitro,and the inhibitory effect and cell survival rate of the compounds on a variety of tumor cell lines were determined by MTT method.Result:Angelicalactone-derived spiropyrazoline analogs 3a-3f was successfully synthesized,and the compound structure was characterized by ^(1)H-NMR,^(13)C-NMR,and MS-ESI.The experimental results showed that 3c had a significant inhibitory effect on HCT116 and RKO,and 3d had a significant inhibitory effect on MDA-MB-231.Conclusion:The preparation of angelicalactone-derived spiropyrazoline analogs has potential anticancer activity.

关 键 词：癌症 中药当归抗癌 当归内酯衍生物 

分 类 号：R285.5[医药卫生—中药学]