Conventional and Microwave-Assisted CuAAC Synthesis of Novel Sulphadimidine–1,2,3-Triazole Hybrids: Spectral Characterization, ADMET Analysis and Antimicrobial Evaluation

Abstract

A series of novel sulphadimidine–1,2,3-triazole hybrid derivatives (6a-o) was synthesized through copper-catalysed azide–alkyne cycloaddition (CuAAC) reactions under both conventional and microwave-assisted conditions. The synthetic approach involved N-propargylation of sulphadimidine followed by regioselective cycloaddition with various aromatic azides to afford 1,4-disubstituted 1,2,3-triazole derivatives in good to excellent yields. Reaction optimization demonstrated that microwave-assisted synthesis significantly enhanced reaction efficiency by reducing reaction time from several hours to a few minutes while improving product yields up to 97%. The synthesized compounds were characterized using FT-IR, ¹H NMR, ¹³C NMR, mass spectrometry and elemental analysis, confirming the successful formation of the target sulphadimidine–triazole framework. The lipophilicity and in silico ADMET properties of the synthesized derivatives were evaluated using the SwissADME platform. Most compounds exhibited acceptable lipophilic behaviour with moderate log P values, although high molecular weights and elevated TPSA values suggested limited oral bioavailability for certain derivatives. Antimicrobial screening revealed moderate antibacterial activity against selected bacterial strains, whereas antifungal activity was comparatively weaker. Among the tested derivatives, compounds 6b, 6e and 6k demonstrated relatively improved antibacterial activity, while compound 6c exhibited comparatively better antifungal activity against Candida albicans, Aspergillus niger and Aspergillus clavatus. The study demonstrates that structural modification of sulphadimidine through triazole incorporation provides promising hybrid scaffolds for further optimization toward biologically active antimicrobial agents.