Li Yong, Wu Taotao, Chen Guobin, He Jian, Zhang Yong, Zhang Qin, Zhou Pengfei, Chen Wenzhang, Fan Lingling
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine &, School of Pharmaceutical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, 550004, People's Republic of China.
Mol Divers. 2025 Sep 12. doi: 10.1007/s11030-025-11348-7.
Twenty-eight novel phthalide derivatives incorporating thiazole, 1,3,4-oxadiazole, and oxime ether moieties were designed and synthesized using a pharmacophore hybridization strategy. Bioactivity assays demonstrated that compounds 1b, 1c, 4a, 4b and 4c exhibited moderate to excellent inhibitory activity against several specific fungi. Notably, compound 1b displayed superior antifungal efficacy against F. solani, F. oxysporum, B. dothidea, and V. mali compared to the commercial fungicides hymexazol and boscalid, with EC values of 15.0 μg/mL, 10.0 μg/mL, 6.1 μg/mL, and 11.4 μg/mL, respectively. Additionally, compound 1b provided superior protective efficacy against B. dothidea-infected apples compared to boscalid. Preliminary mechanistic studies revealed that compound 1b could exert its antifungal activity by compromising the integrity of the hyphal cell membrane. This study highlights the potential of phthalide derivatives bearing dihalocarbonyl and oxime moieties as effective antifungal agents for controlling plant pathogenic fungi, warranting further investigation in the future.
采用药效团杂化策略设计并合成了28种含有噻唑、1,3,4-恶二唑和肟醚部分的新型邻苯二甲酸酯衍生物。生物活性测定表明，化合物1b、1c、4a、4b和4c对几种特定真菌表现出中等至优异的抑制活性。值得注意的是，与市售杀菌剂噁霉灵和啶酰菌胺相比，化合物1b对茄丝核菌、尖孢镰刀菌、苹果黑腐皮壳菌和苹果轮纹病菌表现出更高的抗真菌效力，其EC值分别为15.0 μg/mL、10.0 μg/mL、6.1 μg/mL和11.4 μg/mL。此外，与啶酰菌胺相比，化合物1b对苹果黑腐皮壳菌感染的苹果具有更高的保护效力。初步机理研究表明，化合物1b可通过破坏菌丝细胞膜的完整性发挥其抗真菌活性。本研究突出了含有二卤代羰基和肟部分的邻苯二甲酸酯衍生物作为控制植物病原真菌的有效抗真菌剂的潜力，值得未来进一步研究。
