含偕二甲基环丙烷结构的1,3,4-噻二唑-脲化合物的合成、抑菌活性及分子对接研究  

Synthesis,Antifungal Activity and Molecular Docking Study of 1,3,4-Thiadiazole-Urea Compounds Containing gem-Dimethylcyclopropane Ring Structure

作　　者：崔玉成 陈美桦 林桂汕[1] 段文贵[1] 李晴敏 邹壬萱 岑波[1] Cui Yucheng;Chen Meihua;Lin Guishan;Duan Wengui;Li Qingmin;Zou Renxuan;Cen Bo(School of Chemistry and Chemical Engineering,Guangxi University,Nanning 530004)

机构地区：[1]广西大学化学化工学院,南宁530004

出　　处：《有机化学》2022年第11期3784-3797,共14页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.31870556);广西大学生创新创业训练计划(No.202110593182)资助项目。

摘　　要：为了寻找以天然可再生资源为基础的杀菌剂,设计并合成了18个新型含偕二甲基环丙烷结构的1,3,4-噻二唑-脲化合物.在质量浓度为50 mg/L时,初步测定了目标化合物对6种植物病原菌的抑菌活性.结果表明,(+)-顺-1-(4-溴苯基)-3-{5-[(2,2-二甲基-3-丙基环丙基)甲基]-1,3,4-噻二唑-2-基}脲(7i)对西瓜炭疽病菌、玉米小斑病菌和番茄早疫病菌的抑制率分别为91.2%、85.0%和60.1%,均高于阳性对照百菌清.此外,采用比较分子力场分析法(Co MFA)建立了一个合理有效的三维定量构效关系(3D-QSAR)模型(r^(2)=0.990,q^(2)=0.517);通过分子对接探究了目标化合物与琥珀酸脱氢酶之间的作用模式,并定量分析了其中关键的Arg残基与苯环之间的阳离子-π相互作用;前线分子轨道计算表明目标化合物中的偕二甲基环丙烷以及噻二唑-脲-苯结构可能对抑菌活性起主要贡献.In an attempt to search for natural renewable product-based antifungal agents,eighteen 1,3,4-thiadiazole-urea compounds containing gem-dimethylcyclopropane ring structure were designed and synthesized.The antifungal activity of the target compounds against six plant pathogens was preliminarily evaluated at the concentration of 50 mg/L.As a result,the inhibitory rates of(+)-cis-1-(4-bromophenyl)-3-(5-((2,2-dimethyl-3-propylcyclopropyl)methyl)-1,3,4-thiadiazol-2-yl)urea(7i)against Colletotrichum orbicular,Bipolaris maydis and Alternaria solani were 91.2%,85.0%and 60.1%,respectively,which was better than that of the positive control chlorothalonil.Furthermore,a reasonable and effective 3D-quantitative structure-activity relationship(3D-QSAR)model(r^(2)=0.990,q^(2)=0.517)was established by the comparative molecular field analysis method(CoMFA).The binding mode between the target compounds and succinate dehydrogenase(SDH)was investigated by molecular docking,and the cation-πinteraction between the key residue Arg and the benzene ring was quantitatively analyzed.The gem-dimethylcyclopropane and thiadiazole-urea-benzene moieties of the target compounds probably made major contributions to the antifungal activity by frontier molecular orbital calculation.

关 键 词：3-蒈烯 偕二甲基环丙烷 1 3 4-噻二唑-脲 抑菌活性 三维定量构效关系(3D-QSAR) 分子对接 

分 类 号：TQ455.4[化学工程—农药化工]