Synthesis of Diphenyl Sulfonamide Derivatives as Potential Inhibitors ofV-ATPase

Introduction: Sulfonamide compounds are widely used in pesticide chemistry. This study aims to synthesize novel diphenyl sulfonamide derivatives with improved pesticidal properties. Materials and Methods: Fifty-five diphenyl sulfonamide derivatives were designed and synthesized using Suzuki, Wittig, and Sonogashira couplings, as well as propargyl etherification. The compounds were characterized by spectroscopic techniques, and their insecticidal activities against Mythimna separata were evaluated. Their mechanisms of action were further explored through electrophysiological tests using a Drosophila melanogaster model and molecular docking analyses. Results: Compounds S6-3 and S6-4 demonstrated high insecticidal activity, with LC₅₀ values of 0.474 and 0.401 mg/mL, respectively, both superior to L-1. S6-4 affected Drosophila melanogaster neuromuscular junctions in a manner similar to bafilomycin A1, and molecular docking indicated binding to the H subunit of V-ATPase. Discussion: Structure-activity relationship analysis revealed the key structural features influencing insecticidal activity, providing guidance for further compound optimization. Conclusion: The synthesized derivatives targeting V-ATPase exhibited potent insecticidal activity and showed strong potential for the development of novel pesticides.