Biological Applications and Synthesis of 1,2,3-triazole Linked Six Membered Fused N-heterocycles

In recent years, significant progress has been achieved in the synthesis of six-membered N-heterocycle-fused hybrids, particularly derivatives of quinoline, quinazoline, quinoxaline, and isoquinoline linked with triazole rings. These hybrid molecules are predominantly synthesized through efficient click chemistry techniques using variety of copper salts like CuSO₄, CuI, Cu(OAc)₂, and sodium ascorbate as reducing agent to efficiently link azides and alkynes, facilitating an efficient production of target compounds. N-heterocycles are well-known for their diverse biological activities and their conjugation with triazole moieties has further expanded the potential for discovering novel, potent bioactive agents. This review offers a comprehensive analysis of research advancements in the past 15 years, emphasizing the synthesis, structural diversity, and biological applications of these fused heterocyclic-triazole hybrids. Focus is given to their evaluated biological activities, including antimicrobial, antimalarial, anticancer, antifungal, antiviral, and enzyme inhibition etc., assessed through in vitro assays as well as computational techniques. Significant outcomes indicate strong anticancer effects across multiple cell lines, including HCT-116, MCF-7, and HeLa. Along with that, electron-withdrawing groups like fluorine or chlorine significantly enhanced anticancer and antimicrobial activity. Best nine leads were filtered out from various biological activities with IC₅₀ values ranging from 0.04 to 3.67 µM. The insights presented here highlight the immense therapeutic potential of these compounds and their importance as promising candidates for future drug development, thereby providing a valuable resource for researchers aiming to explore new avenues in bioactive heterocyclic chemistry.