1,2,3-Triazole hybrids in medicinal chemistry: Advances in click chemistry and cytotoxic studies

Abstract

The 1,2,3-triazole ring, a key pharmacophore among nitrogen-containing heterocycles, has garnered significant attention due to its versatility and broad pharmacological applications. These five-membered heterocyclic motifs, containing three nitrogen heteroatoms, are easily synthesized via copper- or ruthenium-catalyzed azide-alkyne cycloaddition reactions (CuAAC and RuAAC), hallmark processes of ‘click chemistry.’ The unique ‘linker’ property of 1,2,3-triazoles has enabled the development of a novel class of hybrids and conjugates, expanding the chemical space of bioactive molecules. Recent advancements in medicinal chemistry have demonstrated the efficacy of these compounds as potential therapeutic agents with diverse biological activities, including anticancer, antimicrobial, antiviral, anti-tubercular, antidiabetic, antimalarial, anti-leishmanial, and neuroprotective properties. Additionally, the DNA-binding affinity of certain hybrids underscores their role in targeted therapies. This review highlights the synthesis, structural optimization, and biological evaluation of 1,2,3-triazole-containing hybrids and conjugates published since 2018, emphasizing their potential as lead compounds for drug discovery. Furthermore, we explore structure-activity relationships (SARs), synthetic methodologies, and emerging trends in 1,2,3-triazole research. The insights provided will be valuable to researchers in the fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology, guiding future innovations in therapeutic development.