天然stilbene导向的取代苯乙烯基噻唑化合物的合成和生物活性  

Synthesis and Biological Activity of Natural Stilbene-Inspired Substituted Styrylthiazole Derivatives

作　　者：章俊辉 朱亚波[1] 翁建全[1] 余茜 袁静 陈杰[3] Zhang Junhui;Zhu Yabo;Weng Jianquan;Yu Qian;Yuan Jing;Chen Jie(College of Chemical Engineering,Zhejiang University of Technology,Hangzhou 310032;Clinical Pharmacy(School of Integrative Pharmacy,Institute of Integrative Pharmaceutical Research),Guangdong Pharmaceutical University,Guangzhou 510006;Collaborative Innovation Center of Green Pesticide,Zhejiang A&F University,Hangzhou 311300)

机构地区：[1]浙江工业大学化学工程学院,杭州310032 [2]广东药科大学临床药学院(整合药学院、整合药学研究院),广州510006 [3]浙江农林大学绿色农药协同创新中心,杭州311300

出　　处：《有机化学》2020年第4期1055-1061,共7页Chinese Journal of Organic Chemistry

基　　金：浙江省自然科学基金(No.LY17C140003)资助项目.

摘　　要：为了寻找新型结构的药物先导化合物,基于天然stilbenes骨架结构,将含氟苯基噻唑环结构与其相杂合,设计合成了一系列新型取代苯乙烯基噻唑类化合物.所有目标化合物结构均经1H NMR、13C NMR和ESI-HRMS表征确证.离体真菌抑制活性结果表明,在100 mg/L浓度下部分化合物对小麦赤霉病菌、玉米小斑病菌和黄瓜蔓枯病菌表现出中等抑制活性,其中(E)-5-溴-4-(2,6-二氟苯基)-2-(4-三氟甲基苯乙烯基)噻唑(6p)对小麦赤霉病菌的抑制率达到86.7%;采用Top1介导的DNA松散实验测试了化合物对拓扑异构酶I(Top1)的抑制活性,结果表明在50μmol L^-1浓度下,所有化合物对Top1均表现出一定程度的抑制活性,其中(E)-5-溴-4-(2,6-二氟苯基)-2-(2-氯苯乙烯基)噻唑(6k)的抑制活性较好,其在0.2μmol L^-1浓度下仍对Top1呈现出一定程度的抑制活性.In order to find novel drug leads,a series of natural stilbene-inspired substituted styrylthiazole derivatives were designed and synthesized by hybridization of the structures of both bioactive 2,6-difluorophenylthiazole moiety and stilbene.The structures of the title compounds were confirmed by 1H NMR,13C NMR and ESI-HRMS.The in vitro antifungal bioassay results indicated that some compounds showed moderate inhibition activity against FusaHum graminearum,Helminthosporium maydis and Mycosphaerella melonis at 100μg/mL,and the inhibition rate of(E)-5-bromo-4-(2,6-difluorophenyl)-2-(4-trifluoromethylstyryl)thiazole(6p)against FusaHum graminearum reached 86.7%.These compounds were also screened for their topoisomerase I inhibitory activity using Top1-mediated relaxation assay.The results showed that all of them exhibited certain Top1 inhibitory activity at 50μmol L^-1,and amongst them(E)-5-bromo-4-(2,6-difluorophenyl)-2-(2-chlorostyryl)thiazole(6k)displayed promising Top1 inhibitory activity,which still remained certain activity at 0.2μmol L^-1.

关 键 词：二苯乙烯 苯乙烯基噻唑 合成 生物活性 

分 类 号：TQ463[化学工程—制药化工]