Molecular docking and SARs guiding the gradual development of thiazole‐2‐yl amide derivatives containing biphenyl groups as promising antifungal scaffolds

作者：Xiang Cheng, Chao Zhang, Fanglei Wang, Yiyang Shao, Shichen Li, Rong Li, Yuting Hu, Xiaoxiao Qian, Qianqian Wei, Dandan Wang, Xianhai Lv, Xihao Chang · 发表于：Pest Management Science · 年份：2025 · DOI：10.1002/ps.70108 · 被引用次数：7 · 研究领域：Fungal Plant Pathogen Control、Plant Disease Resistance and Genetics、Synthesis and biological activity

Abstract BACKGROUND The antifungal activities ofthe initially synthesized thiazol‐2‐ylbenzamide derivatives were relatively limited, suggesting potential for structural optimization. Inspired by the promising bioactivities of biphenyl scaffolds, and guided by molecular docking and structure–activity relationships (SARs), 42 thiazol‐2‐ylamide derivatives containing a biphenyl scaffold were synthesized through gradual structural modification, and their antifungal and anti‐oomycete activities were assessed. Furthermore, the most potent compound G41 was selected for preliminary mechanistic studies. RESULTS Bioassay results indicated that compound G41 [half maximal effective concentration (EC 50 ) values of 0.16, 0.20, 0.23, 0.11,] and 0.28 mg L −1 , respectively] exhibited broader antifungal spectrum and stronger effects against Sclerotinia scleotiorum , Botrytis cinerea , Fusarium graminearum , Pythium graminicola and Curvularia lunata than boscalid (EC 50 values of 0.16, 0.93, >10, >10 and 0.35 mg L −1 , respectively) and thifluzamide (EC 50 values of 0.97, >10, >10, >10 and 3.14 mg L −1 , respectively). Additionally, treatment with compound G41 (100 mg L −1 ) effectively suppressed further infection by B. cinerea on cherry tomatoes. Preliminary mechanistic investigations demonstrated that compound G41 significantly altered the hyphal surface morphology and compromised the cellular ultrastructure of B. cinerea , leading to severe damage to the fungal cell membran...