Synthesis and Evaluation of Novel 1-Methyl-1H-pyrazol-5-amine Derivatives with Disulfide Moieties as Potential Antimicrobial Agents.

Abstract

Sulfur-containing compounds have diverse biological functions and are crucial in crop protection chemistry. In this study, a series of novel 1-methyl-1H-pyrazol-5-amine derivatives incorporating disulfide moieties were synthesized and evaluated for their antimicrobial properties. In vitro bioassays demonstrated that compound 7f displayed potent antifungal activity against Valsa mali, with an EC50 value of 0.64 mg/L, outperforming allicin (EC50 = 26.0 mg/L) but lower than tebuconazole (EC50 = 0.33 mg/L). In vivo experiments confirmed that compound 7f could effectively inhibit V. mali infection on apples at a concentration of 100 mg/L, similar to the positive control tebuconazole. Mechanistic studies revealed that compound 7f could induce hyphal shrinkage and collapse, trigger intracellular reactive oxygen species accumulation, modulate antioxidant enzyme activities, initiate lipid peroxidation, and ultimately cause irreversible oxidative damage to the cells of V. mali. Additionally, compound 7b exhibited notable antibacterial activity, particularly against Pseudomonas syringae pv. actinidiae, with a MIC90 value of 1.56 mg/L, surpassing the positive controls allicin, bismerthiazol, and streptomycin sulfate. These findings suggest that 1-methyl-1H-pyrazol-5-amine derivatives containing disulfide moieties hold promise as potent candidates for the development of novel antimicrobial agents.