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Triazole-Sulfonamide Hybrids as Carbonic Anhydrase Inhibitors: Emerging Chemistry and Bioactivity Insights From 2020
Mohamed S Nafie1,2,3, Heba F Ashour4, Sherif Ahsraf Fahmy5
1Department of Chemistry, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Abstract:
The development of triazole-sulfonamide hybrids is an emerging frontier in medicinal chemistry, combining the clinically validated sulfonamide core with a triazole linker. This structural synergy has yielded potent and selective carbonic anhydrase inhibitors (CAIs) targeting various human and mycobacterial isoforms. Besides CA inhibition, these hybrids also exhibit multi-target binding. They can also interact with vascular endothelial growth factor receptor-2 (VEGFR-2), telomerase, and other oncological and microbial targets, highlighting their broader therapeutic potential against cancer, tuberculosis, and neuropathic diseases. This review provides an overview of synthetic methods, structure-activity relationships (SAR), and isoform selectivity of triazole-sulfonamide conjugates reported from 2020 to 2025. Unlike other reviews focused on CA inhibitory properties, we highlight the multi-inhibitor pharmacological profile of these hybrids and demonstrate their applications in multi-target drug design.
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