Design,synthesis,and biological evaluation of a series of novel cordycepin derivatives  

一系列新型虫草素衍生物的设计、合成及其抗肿瘤活性研究

作　　者：Lijuan Jiang Tingting Cao Ruoyi Yang Ying Li Lin Dong Shufan Yin 蒋丽娟;曹婷婷;杨诺一;李颖;董林;尹述凡(广西民族大学化学化工学院广西多糖材料与改性重点实验室,广西南宁530008;四川大学化学学院,四川成都610064)

机构地区：[1]College of Chemistry,Sichuan University,Chengdu 610064,Sichuan,China [2]School of Chemistry and Chemical Engineering,Guangxi University for Nationalities,Guangxi Key Laboratory for Polysaccharide Materials and Modifications,Nanning 530008,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2022年第1期55-67,共13页中国药学（英文版）

基　　金：Research Basic Ability Enhancement Project of Young and Middle-aged Teachers in Guangxi Universities(Grant No.2019KY0166);the Project of Guangxi University for Nationalities(Grant No.2018MDYB006,2018XJGY46)。

摘　　要：In this study,a novel series of cordycepin derivatives with benzenesulfonamido groups at the 6-position of the purine ring were synthesized and their antitumor activity was evaluated.We revealed the structural moieties of the cordycepin analogs that were required for antitumor activity.Among all the target compounds,those with 4-methyl and 4-nitro substituents on the benzene ring displayed better activity than the lead compound in antiproliferative activity experiments using MDA-MB-231 and A549 cells.However,compounds with 4-methoxybenzene and 2-oxoindoline groups and ethylene spacers displayed more significant activity than the lead compound in antiproliferative activity experiments using He La cells.In particular,a compound with a 4-bromo substituent and an ethylene spacer displayed very high inhibitory activity against the proliferation of MDA-MB-231,A549,and He La cells,suggesting that it had the potential for further development and application.本研究合成了一系列6位嘌呤环取代苯磺酰胺基团的虫草素衍生物,并对其进行了抗肿瘤活性研究。我们对虫草素衍生物具有抗肿瘤活性的药效结构部分做了初步探讨。在MDA-MB-231和A549细胞的抗增殖活性实验中,苯环上有4-甲基和4-硝基取代基的化合物活性优于先导化合物。然而,在HeLa细胞的抗增殖活性实验中,4-甲氧基苯、2-氧吲哚啉基团化合物和乙烯基的化合物活性比先导化合物表现出更显著的活性。其中,具有4-溴取代基的化合物3e和3f对MDA-MB-231、A549和HeLa细胞的增殖均具有很高的抑制活性,这意味着它具有进一步开发和应用的潜力。

关 键 词：CORDYCEPIN DERIVATIVES SYNTHESIS Biological activity research 

分 类 号：R916[医药卫生—药学]