eChapter Name: 1,2,3-Triazole, an Emerging Heterocyclic Scaffold: An overview of Synthesis and Bioactivities
9789372193862
eBook Name: FRONTIERS IN ORGANIC CHEMISTRY RESEARCH AND ADVANCES
by Rama Kanwar Khangarot, Gangotri Pemawat
Introduction
Heterocyclic chemistry is advancing rapidly, driven by its diverse applications and crucial role in drug discovery (Kabir & Uzzaman, 2022; Vala et al., 2022). Among various heterocycles, nitrogen and oxygen-containing compounds such as pyrazoles, thiazoles, and triazoles are especially notable for their potent biological activities (Li Petri et al., 2020). These compounds play a key role in addressing diseases caused by microbes, resistant strains, and genetic mutations. Advances in synthetic methods have enabled the development of vast heterocyclic libraries essential for drug screening. Remarkably, heterocyclic frameworks account for nearly 75% of modern low molecular-weight drugs, highlighting their significance in medicinal chemistry (“Thematic Issue ‘Heterocyclic Compounds in Medicinal Chemistry, 2020). Within this context, 1,2,3-triazole has gained significant attention due to its exceptional stability under oxidative, reductive, and hydrolytic conditions, as well as its efficient and regioselective synthesis (Vaishnani et al., 2024). Its unique structural features such as lipophilicity, polarity, rigidity, and favorable pharmacological properties along with strong binding affinity to biomolecular targets, make it an indispensable scaffold in bioactive heterocycles (Devasia et al., 2022). Moreover, 1,2,3-triazole has been used as a bioisostere in medicinal chemistry, aiding the development of pharmaceutical drugs. 1,2,3-Triazoles display a wide array of therapeutic activities, including antiepileptic (Pålhagen et al., 2001), anti-platelet (Campos et al., 2009), anti-microbial (Baddam et al., 2024; El Malah et al., 2020; Mendapara et al., 2024), anti-viral (Farghaly et al., 2024; Gadali et al., 2024; Sabt et al., 2024), anti-inflammatory (Ambala et al., 2024; Awasthi et al., 2024; Qi et al., 2024), anti-cancer (Belay et al., 2024; Bimoussa et al., 2024; Duan et al., 2024; Meenakshy et al., 2024), anti-leishmanial (Molaei et al., 2024; Rodrigues Gazolla et al., 2024), antiplasmodial (A. Yadav et al., 2024; J. Yadav & Kaushik, 2024), anti-alzheimer (Shareghi-Boroujeni et al., 2024), and anti-HIV (Alvarez et al., 1994; Feng et al., 2021; Lazrek et al., 2001) effects. They also act as enzyme inhibitors (Dhameja et al., 2022; El-Naggar et al., 2024; G. Kumar et al., 2024; A. Singh et al., 2024; M. Singh et al., 2024), and anti-convulsants, and protect against snake venom (Ornellas et al., 2024; Simas Pereira Junior et al., 2024). Notably, approved drugs containing 1,2,3-triazole include tazobactam (ß-lactamase inhibitor), cefatrizine (anti-bacterial), and rufinamide (anti-convulsant) (Figure 1).