Design, synthesis, antifungal activity, and molecular docking of novel trifluoromethyl pyrimidine derivatives containing 1,3,4‐oxadiazole and thioether moieties as potential succinate dehydrogenase inhibitors

Abstract

AbstractSuccinate dehydrogenase (SDH), a pivotal enzyme linking the respiratory electron transport chain and tricarboxylic acid (TCA) cycle, has been identified as an ideal target for developing effective fungicides. In this study, 20 novel trifluoromethyl pyrimidine derivatives containing 1,3,4‐oxadiazole and thioether moieties were prepared and characterized their structures by 1H NMR, 13C NMR, and HRMS. Bioassay results showed that some of the target compounds revealed moderate to good in vitro antifungal activities toward Rhizoctonia solani (R. solani), Botryosphaeria dothidea (B. dothidea), Phomopsis sp., Botrytis cinerea (B. cinerea), Fusarium oxysporum (F. oxysporum), Sclerotinia sclerotiorum (S. sclerotiorum), Phytophthora infestans (P. infestans), and Magnaporthe oryzae (M. oryzae). In particular, compounds 6g and 6i had better in vitro antifungal activity against B. cinerea, with the EC50 values of 19.43 and 28.22 μg/mL, respectively, than that of Pyrimethanil (57.30 μg/mL). As well, compound 6r exhibited good in vitro antifungal activity against F. oxysporum, with the EC50 value of 3.61 μg/mL, which were lower than that of Boscalid (0.40 μg/mL). In addition, the molecular docking simulation revealed that compound 6r interacted with GLN‐150, ASP‐153, LYS‐151, GLY‐154, and GLY‐228 of SDH through hydrogen bond, which could explain the probable mechanism of action between the target compounds and SDH. This is the first report on the antifungal activity of novel trifluoromethyl pyrimidine derivatives containing 1,3,4‐oxadiazole and thioether moieties as potential SDH inhibitors.