To discover new antimicrobial agents, a series of new benzohydrazide derivatives containing 4-aminoquinazoline and chalcone moieties were designed and synthesized through a pharmacophore hybridization strategy. The bioassay results demonstrated that many derivatives exhibited potent in vitro antimicrobial efficacies against the tested phytopathogenic fungi and bacteria. Particularly, the EC50 value of compound C25 was 0.81 μg/mL against Rhizoctonia solani, close to Carbendazim but superior to Chlorothalonil/Boscalid. In vivo bioassays confirmed the efficacy of this compound, giving pronounced curative and protective activities against R. solani infected rice plants. The mechanistic studies indicated that compound C25 compromised cytomembrane integrity, inhibited fungal SDH from R. solani (IC50 = 10.3 μM), and bound to active sites of SDH as revealed by molecular docking. Besides, compound C8 demonstrated a remarkable antibacterial effect against Xanthomonas axonopodis pv citri (EC50 = 8.51 μg/mL). Overall, this study showcases the potential of the discussed benzohydrazide derivatives as effective antimicrobial agents.
Li et al. (Wed,) studied this question.