Synthesis of Chalcone Derivatives and Studies on Their Inhibitory Activity and Molecular Docking

Twenty nine chalcone derivatives were designed, synthesized and characterized by IR, H-1 NMR, C-13 NMR and HRMS. The antifungal activities of all the synthesized compounds were determined against five plant pathogenic fungi namely Rhizoctonia solani, Fusarum graminearum, Helminthosporium maydis, Sclerotinia sclerotiorum and Botrytis cinerea. Preliminary results indicated that most of them revealed significant antifungal activity. Among them, (E)-N-(4-(3-(5-bromothiophen-2-yl)acryloyl)phenyl)nicotinamide (4m) (EC50 = 0.057 mg/L) and (E)-2-hydroxy-N-(4-(3-(pyridin-3-yl)acryloyl)phenyl)acetamide (6i) (EC50 =0.054 mg/L) showed the strongest activities against S. sclerotiorum and possessed better antifungal activities than the commercial fungicide of fluopyram (EC50 =0.244 mg/L). Meanwhile, the inhibitory activities of compounds 4m and 6i were tested against succinate dehydrogenase (SDH). The results displayed that they had also better activities than fluopyram. Molecular docking studies demonstrated that compounds 4m and 6i bound well to SDH and their binding energies were -31.0 and -31.4 kJ/mol, respectively. Moreover, compounds 4m and 6i formed hydrogen bonds with residue B/Trp-230 of SDH, respectively.