Design, Synthesis, and 3D-QASR of 2-Ar-1,2,3-triazole Derivatives Containing Hydrazide as Potential Fungicides

Abstract

A series of novel 2-Ar-1,2,3-triazole derivatives were designed and synthesized based on our previously discovered active compound <b>6d</b> against <i>Rhizoctonia solani</i>. Most of these compounds exhibited good antifungal activity against <i>R. solani</i> at a concentration of 25 μg/mL. Based on the results of biological activity, we established a three-dimensional quantitative structure-activity relationship (3D-QSAR) model that guided the synthesis of compound <b>7y</b>. Compound <b>7y</b> exhibited superior activity against <i>R. solani</i> (EC₅₀ = 0.47 μg/mL) compared to the positive controls hymexazol (EC₅₀ = 12.80 μg/mL) and tebuconazole (EC₅₀ = 0.87 μg/mL). Furthermore, compound <b>7y</b> demonstrated better protective activity than the aforementioned two commercial fungicides in both detached leaf assays and greenhouse experiments, achieving 56.21% and 65.75% protective efficacy, respectively, at a concentration of 100 μg/mL. The ergosterol content was determined and molecular docking was performed to explore the mechanism of these active molecules. DFT calculation and MEP analysis were performed to illustrate the results of this study. These results suggest that compound <b>7y</b> could serve as a novel 2-Ar-1,2,3-triazole lead compound for controlling <i>R. solani.</i>