Research Article

Design, Synthesis, and Biological Activity of Novel 1,2,3-Triazole Hybrids as Potent Antimicrobial

Abstract

Antimicrobial resistance (AMR) and biofilm-associated infections remain core drivers of the global health crisis. New antimicrobial scaffolds that can deliver enhanced efficacy with low toxicity are needed [1]. A series of rationally designed indole 1,2,3-triazole hybrid derivatives (3ta-3te) were synthesized via efficient N-propargylation followed by Cu(I)-catalyzed azide-alkyne cycloaddition or click reaction. The structure was elucidated by IR, 1H & 13C NMR plus melting point analysis which confirmed successful formation of the targeted hybrids. Antibacterial/antibiofilm activities against S.aureus & B.subtilis/E.coli revealed that sulfonamide containing derivatives; 3td & most potently active te exhibited MIC values as low as 6.21μ M coupled with strong bactericidal effects! Molecular docking on S.aureus 4DUH showed high binding affinity scores (-8.07 to -8.39 kcal mol−1) for both compounds where they formed important H bond/ π-cation interactions (ARG136 catalytic residue) & ASP73 with biological results ADMET profiling highlighted positive physicochemical, pharmacokinetic and drug-likeness properties associated with oral administration among which 3te can be considered as a potential lead candidate. The results of the present study revealed that hybridization of triazole and indole pharmacophores  resulted in enhanced antibacterial and antibiofilm activity, hence establishing them as scaffold platforms for next-generation antimicrobial agents.