Novel 5,6-dihydrobenzo[h]quinazoline derivatives as succinate dehydrogenase inhibitors: design, synthesis, antifungal activity and mechanism of action

BACKGROUNDThe growing problem of resistance to plant pathogenic fungi poses a serious threat to the quality and safety of crops worldwide. Antifungal agrochemicals have been effective in significantly reducing the incidence of plant diseases caused by pathogenic fungi as an economical and efficient control strategy.RESULTSIn the present study, 36 novel azoles containing the structure of 5,6-dihydrobenzo[h]quinazoline were designed and successfully synthesized. It was found that most of the target compounds showed good inhibitory effects against phytopathogenic fungi at a concentration of 30 mu g mL-1. Thus, the compounds were used in the study of the plant pathogenic fungi. Compounds 5g, 5h, 5m, 8e, 8g, 8i, 8o, 8p, 8q and 8r showed excellent inhibitory effects on Rhizoctonia solani, with inhibition rates of more than 90%. Among them, the inhibition rates of compounds 8e, 8q and 8r reached 100%. Further experiments showed that the half-maximal effective concentration (EC50) values of 8e, 8q and 8r were 0.185, 0.298 and 0.323 mu g mL-1, respectively, which were significantly better than those of fluquinconazole (EC50 = 0.478 mu g mL-1). In the inhibitory activity study of succinate dehydrogenase (SDH), compounds 8e, 8q and 8r also showed excellent performance, with half-maximal inhibitory concentration (IC50) values of 0.218, 0.304 and 0.382 mu g mL-1, respectively, which were superior to that of fluquinconazole (IC50 = 0.531 mu g mL-1). The fluorescence quenching assay, in vivo curative and protective activities, scanning electron microscopy and transmission electron microscopy of compound 8e, revealed that compound 8e had a better effect than the positive control. In addition, molecular docking experiments elucidated that the mode of action for compound 8e is more similar to fluquinoconazole.CONCLUSIONThis study demonstrated that compounds 8e, 8q and 8r have superior values as succinate dehydrogenase inhibitor candidates, and are worthy of more in-depth research and exploration. (c) 2025 Society of Chemical Industry.