State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry , Nankai University , No. 94, Weijin Road , Nankai District, Tianjin 300071 , P. R. China.
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Nankai University , No. 94, Weijin Road , Nankai District, Tianjin 300071 , P. R. China.
J Agric Food Chem. 2018 Jul 18;66(28):7319-7327. doi: 10.1021/acs.jafc.8b02332. Epub 2018 Jul 5.
A molecular design approach was used in our laboratory to guide the development of imidazole-based fungicides. Based on homology modeling and molecular docking studies targeting the cytochrome P450-dependent sterol 14α-demethylase, 3,4-dichloroisothiazole-based imidazoles showed great potential. Several such compounds were then rationally designed, synthesized, characterized, and their antifungal activities were evaluated. Bioassay results showed that compounds such as ( R)-11, ( R)-12, and ( S)-11 have commendable, broad-spectrum antifungal activities that are comparable to those of commercial products. Based on Q-PCR testing and microscopy observations, the imidazole derivatives affect fungal cell wall formation through the inhibition of the BcCYP51 expression system. These findings strongly suggest that the mode of action of these imidazole compounds is similar to that of tioconazole and imazalil. This report indicates that this molecular design strategy is not only practical but productive.
本实验室采用分子设计方法指导咪唑类杀菌剂的开发。基于针对细胞色素 P450 依赖性甾醇 14α-脱甲基酶的同源建模和分子对接研究，基于 3,4-二氯异噻唑的咪唑类化合物显示出巨大的潜力。然后，我们合理设计、合成、表征了几种此类化合物，并评估了它们的抗真菌活性。生物测定结果表明，（R）-11、（R）-12 和（S）-11 等化合物具有令人赞赏的广谱抗真菌活性，可与商业产品相媲美。基于 Q-PCR 测试和显微镜观察，咪唑衍生物通过抑制 BcCYP51 表达系统来影响真菌细胞壁的形成。这些发现强烈表明这些咪唑化合物的作用模式与噻康唑和抑霉唑相似。本报告表明，这种分子设计策略不仅实用而且富有成效。
