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.
Nafie et al. (Mon,) studied this question.