Triazole Review: A Comprehensive Study of Chemistry, Synthesis, Biological Activity. Pharmacology, Resistance, and Future Directions

Triazoles have five-member ring containing N-heterocycles mainly represented by 1,2,3- and 1,2,4-triazole isomers, and situated at the heart of medicinal, agricultural and synthetic chemistry. This review provides an overview of the existing knowledge and accomplishments in the realm of triazole chemistry, triazole synthetic access, structure – activity relationships, biological activities, pharmacological behaviour, and drug-resistance issues. The 1,2,3-triazole scaffold has a close connection with the copper-catalyzed azide-alkyne cycloaddition, allowing high-yielding, modular, and selective click synthesis. The 1,2,4-triazole nucleus, however, is characteristic of clinical drugs used for antifungal therapy, aromatization inhibitors, etc., owing to the coordination of heme iron in enzyme cytochrome P450. In recent papers from 2020–2026 the focus is on synthetic methods that incorporate triazole, green synthesis, new antiviral and anticancer agents, and computer-aided optimization. However, in vivo validation is not always strong, there is variability in reporting MIC or IC50 values, there are not always enough selectivity-index data available, and there is a lack of resistance. mediated by CYP51 mutations, efflux-pump overexpression, and biofilm formation. Future development should prioritize standardized biological evaluation, safer scalable synthesis, pharmacokinetic validation, artificial-intelligence-assisted design, and resistance-resilient fourth-generation derivatives.