Zhang Ming-Zhi, Jia Chen-Yang, Gu Yu-Cheng, Mulholland Nick, Turner Sarah, Beattie David, Zhang Wei-Hua, Yang Guang-Fu, Clough John
Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, PR China; Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China.
Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, PR China; Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China.
Eur J Med Chem. 2017 Jan 27;126:669-674. doi: 10.1016/j.ejmech.2016.12.001. Epub 2016 Dec 2.
Based on examples of the successful applications in drug discovery of bioisosterism, a series of streptochlorin analogues in which indole has been replaced by other heterocycles has been designed and synthesized, as a continuation of our studies aimed at the discovery of novel streptochlorin analogues with improved antifungal activity. Biological testing showed that most of the indole-replaced streptochlorin analogues were inactive, though compound 6f had a broad spectrum of antifungal activity with significant activity against Alternaria solani. The SAR study demonstrated that indole ring is an essential moiety for the antifungal activity of streptochlorin analogues, promoting the idea of indole ring as a framework that might be exploited in the future.
基于生物电子等排体在药物发现中的成功应用实例，我们设计并合成了一系列用其他杂环取代吲哚的链霉素类似物，作为我们旨在发现具有改进抗真菌活性的新型链霉素类似物研究的延续。生物学测试表明，大多数吲哚取代的链霉素类似物没有活性，尽管化合物6f具有广谱抗真菌活性，对番茄早疫病菌有显著活性。构效关系研究表明，吲哚环是链霉素类似物抗真菌活性的必需部分，这促进了将吲哚环作为未来可能被利用的骨架的想法。
