Synthesis of New Benzohydrazide Derivatives with the 4-Aminoquinazoline and Chalcone Moieties as Effective Antimicrobial Agents in Agriculture

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 <i>in vitro</i> antimicrobial efficacies against the tested phytopathogenic fungi and bacteria. Particularly, the EC₅₀ value of compound <b>C25</b> was 0.81 μg/mL against <i>Rhizoctonia solani</i>, close to Carbendazim but superior to Chlorothalonil/Boscalid. <i>In vivo</i> bioassays confirmed the efficacy of this compound, giving pronounced curative and protective activities against <i>R. solani</i> infected rice plants. The mechanistic studies indicated that compound <b>C25</b> compromised cytomembrane integrity, inhibited fungal SDH from <i>R. solani</i> (IC₅₀ = 10.3 μM), and bound to active sites of SDH as revealed by molecular docking. Besides, compound <b>C8</b> demonstrated a remarkable antibacterial effect against <i>Xanthomonas axonopodis</i> pv <i>citri</i> (EC₅₀ = 8.51 μg/mL). Overall, this study showcases the potential of the discussed benzohydrazide derivatives as effective antimicrobial agents.