Harnessing coumarin-thio(seleno)cyanate conjugates: potent <i>In vivo</i> antiproliferative agents targeting carbonic anhydrases.

ABSTRACT: We synthesised coumarin-based derivatives bearing thio- and selenocyanates to selectively inhibit tumour-associated carbonic anhydrases (CAs) IX and XII and to exert antiproliferative effects on tumour cells. Structural variations included chalcogen atom type (S, Se), substitutions at C-3/C-4, and tether length at C-7 of the coumarin core. Thiocyanates 4 and 7b showed potent CA IX/XII inhibition (K_i = 17.9-27.4 nM) with >5000-fold selectivity over off-target isoforms (CAs I and II). Selenocyanate 8a exhibited strong antiproliferative activity (GI₅₀ = 0.78-2.6 µM) across six human solid tumour cell lines. Mechanistic studies revealed a cytostatic effect via cell cycle arrest and reduced mitotic progression. In vivo assays in

SUBMITTER: Meza-Ireta SA 

PROVIDER: S-EPMC12604135 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature