Exploring the SAR of 1,2,3-Triazoles as Tumor-Associated Carbonic Anhydrases IX and XII Inhibitors for Anticancer Applications.

The search for novel anticancer agents has brought carbonic anhydrase (CA) isoforms IX and XII into focus due to their critical role in tumor growth and survival, particularly under hypoxic conditions. These tumor-associated enzymes regulate pH and ion transport in cancer cells, making them attractive therapeutic targets. Among the compounds explored as CA inhibitors, 1,2,3-triazoles stand out for their versatile CA inhibition potential and favorable pharmacokinetic properties. 1,2,3-triazole scaffold, easily synthesized via click reactions, offers a promising framework for developing selective inhibitors against CA IX and XII. Recent research highlights the anticancer potential of 1,2,3-triazole derivatives, which selectively inhibit these isoforms, impairing tumor microenvironment regulation and thus enhancing cancer treatment efficacy. The present review explores the structure-activity relationships (SAR) of 1,2,3-triazole scaffolds as tumor-associated CA IX and XII inhibitors. We provide insights into their design and therapeutic potential by examining key structural modifications that enhance potency and selectivity. This comprehensive analysis aims to guide the future development of 1,2,3-triazole-based CA inhibitors for use as antitumor agents.