1,3,4-Oxadiazole Sulfonamide Derivatives Containing Pyrazole Structures: Design, Synthesis, Biological Activity Studies, and Mechanism Study

Abstract

Sulfonamide derivatives have been widely used for pesticide research in recent years. Herein, 1,3,4-oxadiazole sulfonamide derivatives containing a pyrazole structure were synthesized, and their structure–activity relationship was studied. Bioactivity tests showed the remarkable efficacy of most synthesized compounds. Especially for Xanthomonas oryzae pv oryzae, A23 exhibited 100% inhibition at 100 mg/L, surpassing bismerthiazol (99.3%), and 90% inhibition at 50 mg/L, outperforming thiodiazole copper (84.5%), with an EC₅₀ of 5.0 mg/L, markedly more active than bismerthiazol (23.9 mg/L) and thiodiazole copper (63.5 mg/L). Initial investigations into antimicrobial mechanisms involved a series of biochemical analyses, including bacterial growth rate analysis, scanning electron microscopy, bacterial biofilm formation experiments, and molecular docking analyses. Notably, A23 considerably inhibited the formation of Xoo biofilms, disrupting the integrity of bacterial cell membranes. Co-analysis of transcriptomics and proteomics revealed the capability of A23 to regulate pathways such as tryptophan metabolism and phenylpropanoid biosynthesis, enhancing the innate immunity of rice and activating its disease resistance. Thus, A23 emerges as a potential immunoinducible pesticide lead compound for the discovery of highly active immune-inducing agents.