Triazoles as enzyme inhibitors: synthetic advances, mechanism of action, molecular docking studies and structure-activity relationships.

The growing prevalence of drug resistance in microbes urges an immediate need for the development of novel therapeutic agents to serve as multi-target directed ligands. Triazoles belong to a distinctive class of heterocycles that mostly work as multitarget inhibitors and have broad-spectrum antifungal and antibacterial activity. As antifungals triazoles inhibit lanosterol 14α-demethylase (CYP51), whereas, as antibacterials triazoles target DNA gyrase, DHFR (dihydrofolate reductase), PDF (peptide deformylase), FabI (enoyl-ACP reductase), and RNA-associated enzymes, disrupting key microbial pathways. By exploiting the recent synthetic advancements several structurally diverse triazole derivatives and hybrids containing bioactive pharmacophores can be synthesized, with a better inhibitory potential and selectivity. In this paper we report a current landscape of chemical methodologies, highlighting innovative synthetic routes that have streamlined the diversification of this scaffold, including molecular hybridization. To elucidate the molecular mechanisms, experimental findings were correlated with computational insights. This synergy between the synthesis, pharmacological potency, and structural binding affinity, validates the triazoles' potential as a template for the rational design of next-generation antimicrobials.