Molecular strain typing of Trichophyton rubrum indicates multiple strain involvement in onychomycosis.

UNLABELLED: Novel benzenesulfonamide derivatives 2-5 were synthesized via base-catalyzed Claisen-Schmidt condensation and comprehensively evaluated for dual larvicidal efficacy against Wohlfahrtia magnifica and antibacterial activity against multidrug-resistant pathogens. Evaluation against W. magnifica larvae revealed that the thienyl-pyrazole-hybridized 5 exhibited the highest larvicidal potency, driving cumulative mortality to ~92% by day 4 at a concentration of 25 mg/g. Histopathological and ultrastructural analyses confirmed that the treatments caused extensive cuticular breakdown, myofibril fragmentation, severe mitochondrial swelling, and a progressive depletion of the collagen-like extracellular matrix from ~80% down to below 15%. Acridine orange fluorescence staining corroborated treatment-dependent apoptotic nuclear condensation and fragmentation. In antibacterial screenings, the pyrrolidine-pyrazole hybrid 2 exhibited selective, dose-dependent growth inhibition against Gram-negative Klebsiella pneumoniae (inhibition zones: 15-28 mm; MIC: 10 mg/mL) and Escherichia coli (inhibition zones: 9-16 mm; MIC: 25 mg/mL), while showing no activity against Gram-positive Staphylococcus aureus. Scanning electron microscopy (SEM) verified outstanding cell envelope rupture and structural collapse in treated bacteria. In vitro enzyme assays established that compound 2 significantly inhibited E. coli DNA gyrase B (IC50 = 3.188 ± 0.11 µM) and topoisomerase IV (IC50 = 14.288 ± 1.25 µM). Molecular docking simulations demonstrated strong target binding poses within respective ATP-binding cavities with docking scores of -10.88 and -9.98 kcal/mol. In silico ADMET profiling indicated good oral bioavailability, a high human intestinal absorption rate of 94.87%, and a favorable drug-likeness safety window. These quantitative findings identify compound 5 as a potent larvicidal agent and compound 2 as a highly promising multi-target antibacterial lead template for managing resistant Gram-negative infections.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05060-y.