Novel 4,5-dihydro-1H-pyrazole derivatives as potential succinate dehydrogenase inhibitors: design, synthesis, crystal structure, biological activity and molecular modeling

Abstract

Twenty-eight new 4, 5-dihydro-1H-pyrazole derivatives were designed, synthesized and characterized by IR, 1H NMR, 13C NMR and HRMS. The crystal structure of compound 2j was characterized by single crystal X-ray diffraction. Their antifungal activities were evaluated against five plant pathogenic fungi: Coniella diplodiella, Penicillium digitatum, Physalospora piricola, Rhizoctonia cerealis and Sclerotinia sclerotiorum. The results displayed that most of them exhibited significant antifungal activity at 20 µg/mL. Compounds 3a (EC50 = 0.138 µg/mL) and 3f (EC50 = 0.081 µg/mL) exhibited excellent antifungal activity against Sclerotinia sclerotiorum and had better efficacy than the commercial fungicide penthiopyrad (EC50 = 0.250 µg/mL). Meanwhile, the inhibitory activities of the bioactive compounds were determined against succinate dehydrogenase (SDH). The results demonstrated that compounds 3a (IC50 = 0.200 µg/mL) and 3f (IC50 = 0.104 µg/mL) possessed better inhibitory activity than penthiopyrad (IC50 = 0.363 µg/mL). The molecular modeling displayed that compound 3f had stronger affinity to SDH than penthiopyrad. It is the first time that the inhibitory activity of 4,5-dihydro-1H-pyrazole derivatives against SDH has been reported.