Discovery of 2,4-thiazolidinedione-tethered coumarins as novel selective inhibitors for carbonic anhydrase IX and XII isoforms.

ABSTRACT: Different 2,4-thiazolidinedione-tethered coumarins 5a-b, 10a-n and 11a-d were synthesised and evaluated for their inhibitory action against the cancer-associated hCAs IX and XII, as well as the physiologically dominant hCAs I and II to explore their selectivity. Un-substituted phenyl-bearing coumarins 10a, 10 h, and 2-thienyl/furyl-bearing coumarins 11a-c exhibited the best hCA IX (K_Is between 0.48 and 0.93 µM) and hCA XII (K_Is between 0.44 and 1.1 µM) inhibitory actions. Interestingly, none of the coumarins had any inhibitory effect on the off-target hCA I and II isoforms. The sub-micromolar compounds from the biochemical assay, coumarins 10a, 10 h and 11a-c, were assess

SUBMITTER: Eldehna WM 

PROVIDER: S-EPMC8745369 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature