Novel 1,3,4-Oxadiazole-2-carbohydrazides as Prospective Agricultural Antifungal Agents Potentially Targeting Succinate Dehydrogenase.

A novel simple 1,3,4-oxadiazole-2-carbohydrazide was reported to discover low-cost and versatile antifungal agents. Bioassay results suggested that a majority of the designed compounds were extremely bioactive against four types of fungi and two kinds of oomycetes. This extreme bioactivity was highlighted by the applausive inhibitory effects of compounds , , , , , , , , , and against , affording EC values ranging from 0.486 to 0.799 μg/mL, which were superior to that of fluopyram (2.96 μg/mL) and comparable to those of carbendazim (0.947 μg/mL) and prochloraz (0.570 μg/mL). Meanwhile, compounds , , , and showed significant actions against with EC values of 0.652, 0.706, 0.813, and 0.925 μg/mL, respectively. Pharmacophore exploration suggested that the '-phenyl-1,3,4-oxadiazole-2-carbohydrazide pattern is necessary for the bioactivity. Molecular docking of with succinate dehydrogenase (SDH) indicated that it can completely locate the inside of the binding pocket via hydrogen-bonding and hydrophobic interactions, revealing that this novel framework might target SDH. This result was further verified by the significant inhibitory effect on SDH activity. In addition, scanning electron microscopy patterns were performed to elucidate the anti- mechanism. Given these features, this type of framework is a suitable template for future exploration of alternative SDH inhibitors against plant microbial infections.