4-Substituted Pyridine-3-Sulfonamides as Carbonic Anhydrase Inhibitors Modified by Click Tailing: Synthesis, Activity, and Docking Studies.

ABSTRACT: In the search for new selective inhibitors of human carbonic anhydrase (hCA), particularly the cancer-associated isoforms hCA IX and hCA XII, a series of 4-substituted pyridine-3-sulfonamides was synthesized using the "click" CuAAC reaction, proven by X-ray crystallography, and evaluated for their inhibitory activity against hCA I, hCA II, hCA IX, and hCA XII. Additional molecular docking studies and cytostatic activity assays on three cancer cell lines were conducted. The compounds exhibited a broad range of inhibitory activity, with K_I reaching 271 nM for hCA II, 137 nM for hCA IX, and 91 nM for hCA XII. Notably, compound 4 demonstrated up to 5.9-fold selectivity toward the cancer-associated hCA IX over the ubiquitous hCA II, while compound 6 exhibited a remarkab

SUBMITTER: Szafranski K 

PROVIDER: S-EPMC12027749 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature