Design, synthesis, and biological evaluation of novel sulfonamide-linked 1,2,3-triazole conjugates

Triazole-based compounds continue to attract considerable interest in medicinal chemistry, particularly for their diverse antimicrobial potential. In this study, a series of novel 1,2,3-triazole-sulfonamide conjugates (7a-h) were rationally designed and synthesised using the copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) strategy. The synthesised molecules were thoroughly characterised and screened for different anti-microbial activities. Among the series, compound 7h , featuring a 2,5-dichlorophenyl moiety, emerged as the most biologically active candidate, displaying activity against Escherichia coli with an MIC value of 50 µg/mL, Candida albicans with an MIC value of 250 µg/mL, Plasmodium falciparum with an IC₅₀ value of 0.62 µg/mL, and Mycobacterium tuberculosis with an MIC value of 50 µg/mL. SAR analysis revealed that chloro-substitution on the sulfonamide ring plays a critical role in enhancing the biological profiles of the compounds. These results underscore the potential of triazole-sulfonamide hybrids as versatile lead structures for the development of next-generation antimicrobial and antiparasitic therapeutics.