Triazoles as promising small molecules anticancer agents

Shaheen, Mennatallah Ali; Darwish, Khaled Mohamed; Kishk, Safaa; Elsayed, Magda; Salama, Ismail

doi:10.21608/rpbs.2025.400068.1384

Triazoles as promising small molecules anticancer agents

Document Type : Mini-reviews

Authors

¹ Department of Pharmaceutical Chemistry, Horus University, Egypt Department of Medicinal Chemistry, Suez Canal University, Egypt

²  Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.  Department of Medicinal Chemistry, Faculty of Pharmacy, Galala University, New Galala 43511, Egypt

³ a. Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt b. School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK

⁴  Pharmaceutical Chemistry Department, Faculty of Pharmacy, Horus UniversityEgypt  Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

⁵ Faculty of Pharmacy - Suez Canal University

10.21608/rpbs.2025.400068.1384

Abstract

The 1,2,3-triazole scaffold has emerged as a pivotal heterocyclic motif in medicinal chemistry due to its unique physicochemical properties, synthetic accessibility, and broad spectrum of biological activities. These five-membered nitrogen-rich rings are most commonly synthesized via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), a prototypical "click" reaction that offers regioselective access to 1,4-disubstituted triazoles under mild conditions. The resulting triazole ring is chemically stable, metabolically resilient, and capable of mimicking amide bonds, making it a valuable bioisostere in drug design. Biologically, 1,2,3-triazoles have demonstrated diverse pharmacological profiles, including antimicrobial, anticancer, antiviral, anti-inflammatory, and enzyme inhibitory activities. Their ability to engage in hydrogen bonding and π–π stacking interactions enhances their binding affinity to biological targets. Moreover, triazole-containing compounds have been successfully incorporated into peptidomimetics, nucleoside analogs, and targeted drug delivery systems. Recent advances in metal-free and biocompatible triazole synthesis have further expanded their utility in chemical biology and pharmaceutical development. This abstract highlights the dual significance of 1,2,3-triazoles as both versatile synthetic intermediates and potent pharmacophores, underscoring their continued relevance in the discovery and optimization of therapeutic agents.

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