Synthesis of novel phthalide bearing thiazole, 1,3,4-oxadiazole, and oxime ether groups as potential antifungal
Yong Li1, Taotao Wu1, Guobin Chen1
1State 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.
Abstract:
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 EC50 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.
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