Design, Synthesis, and Antifungal Evaluation of ()‐Menthol‐Based 2‐Modified Nicotinamide Derivatives as Potential Succinate Dehydrogenase Inhibitors

ABSTRACT

Twelve novel nicotinamide derivatives incorporating a (‐)‐menthol moiety were designed and synthesized, and their structures were characterized by ¹ H NMR, ¹³ C NMR, and HRMS. The antifungal activities of these new compounds against Rhizoctonia solani , Fusarium solani , Alternaria alternata , and Valsa mali were evaluated. The result indicated that compound 3l displayed potential antifungal activities against these tested fungi at 20 mg/L, with 45.6% and 41.2% inhibition rate toward S. sclerotiorum and V. mali , respectively, whose activities was comparable to or better than commercial fungicides hymexazol. Further EC ₅₀ determination showed that compound 3l exhibited potent inhibitory effects, with values of 45.34 mg/L against V. mali and 47.25 mg/L against S. sclerotiorum . The molecular docking result indicated that 3l was a potential succinate dehydrogenase inhibitor. In addition, preliminary cytotoxicity assays revealed that the representative compound 3l showed low toxicity toward several human normal cell lines under test concentrations. Our study offers a novel perspective on utilizing menthol as a motif in the structural optimization of antifungal compounds.