Design, synthesis and antifungal activity of novel α-methylene-γ-butyrolactone derivatives containing benzothiophene moiety.

BACKGROUND: The discovery of agricultural fungicide candidates from natural products is one of the key strategies for developing environment friendly agricultural fungicides with high efficiency, high selectivity and unique modes-of-action. Based on previous work, a series of novel α-methylene-γ-butyrolactone (MBL) derivatives containing benzothiophene moiety were designed and synthesized. RESULTS: The majority of the proposed compounds displayed moderate to considerable antifungal efficacy against the tested pathogenic fungi and oomycetes, some exhibiting broad spectrum antifungal activity. Notably, compounds 2 (3-F-Ph) and 7 (4-Cl-Ph) showed excellent antifungal activity against Rhizoctonia with half maximal effective concentration (EC50) values of 0.94 and 0.99 mg L-1, respectively, comparable to the commercial fungicide tebuconazole (EC50 = 0.96 mg L-1), and also displayed significant inhibitory effects against V alsa mali with EC50 values of 2.26 and 1.67 mg L-1, respectively - better than famoxadone and carabrone. The in vivo protective and curative effects against R. solani of compound 2 were 57.2% and 53.7% at 100 mg L-1, respectively, which were equivalent to tebuconazole (51.6% and 52.4%). Further investigations found that compound 2 altered the ultrastructure of R. solani cell, significantly increased the relative conductivity of the cells, and reduced the activity of complex III in a dose-dependent manner. Molecular docking results showed that compound 2 matched well with the Qo pocket. CONCLUSION: The results revealed that MBL derivatives containing benzothiophene moiety are promising antifungal candidates and provide a new backbone structure for further optimization of novel fungicides. © 2024 Society of Chemical Industry.