A Comprehensive Review of Triazole as a Privileged Scaffold in Medicinal Chemistry: Advances in Anticancer Drug Discovery
Triazole is a privileged nitrogen-containing heterocyclic scaffold that has attracted much attention in medicinal chemistry because of its remarkable structural diversity, favorable pharmacokinetic properties and wide spectrum of biological activities. The unique electronic properties of 1,2,3-triazole and 1,2,4-triazole rings allow for close interactions with different biological targets, thereby rendering them attractive pharmacophores for rational drug design. In recent years, triazole derivatives have emerged as promising anticancer agents due to their ability to modulate various molecular pathways involved in tumor initiation, progression, metastasis, and drug resistance. The present review summarizes the recent advances in the chemistry, synthetic strategies and the medicinal applications of triazole derivatives with special emphasis on their anticancer potential. The structure–activity relationships of some triazole-based compounds are critically discussed, emphasizing the influence of the structural modifications on the potency, selectivity and pharmacokinetic behavior. Moreover, the molecular mechanisms underlying their anticancer activity are reviewed, including inhibition of protein kinases, tubulin polymerization, DNA topoisomerases, histone deacetylases and other crucial therapeutic targets. Recent advances in hybrid triazole molecules, drug delivery systems based on nanotech¬nology, computational drug design, and clinically relevant triazole-containing compounds are also presented. Finally, the current challenges and future research opportunities and emerging trends in the field of triazole-based anticancer drug discovery are presented. Taken together, this review highlights the importance of triazole as a privileged and versatile scaffold, and provides valuable insights for the rational design and development of next-generation anticancer therapeutics.