Inspired by these findings, we prepared a series of 2,4-thiazolidinedione-tethered coumarins, compounds 5a–b, 10a–n and 11a–d, and evaluated their inhibitory action against the cancer-associated hCAs IX and XII, and selectivity over inhibition of the physiologically dominant hCAs I and II to explore their selectivity in order to the cancer-related isoforms. Here, CYP24A1 is linked to cancer.