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
收稿日期: 2022-04-22
修回日期: 2022-05-31
网络出版日期: 2022-07-14
基金资助
国家自然科学基金(31870556); 广西大学生创新创业训练计划(202110593182)
Synthesis, Antifungal Activity and Molecular Docking Study of 1,3,4-Thiadiazole-Urea Compounds Containing gem-Dimethylcyclopropane Ring Structure
Received date: 2022-04-22
Revised date: 2022-05-31
Online published: 2022-07-14
Supported by
National Natural Science Foundation of China(31870556); College Student Innovation and Entrepreneurship Training Program of Guangxi(202110593182)
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(CoMFA)建立了一个合理有效的三维定量构效关系(3D-QSAR)模型(r2=0.990, q2=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.
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
崔玉成 , 陈美桦 , 林桂汕 , 段文贵 , 李晴敏 , 邹壬萱 , 岑波 . 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[J]. 有机化学, 2022 , 42(11) : 3784 -3797 . DOI: 10.6023/cjoc202204055
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 (r2=0.990, q2=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-π interaction 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.
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