Coumarin-Thiourea Hybrids Show Potent Carbonic Anhydrase IX and XIII Inhibitory Action.

A series of coumarin-thiourea hybrids (4 a-o) has been synthesized, and the compounds have been evaluated against the tumour associated transmembrane isoform, human (h) carbonic anhydrase (CA) hCA IX and the less-explored cytosolic isoform, hCA XIII. All compounds exhibited potent inhibition of both isoforms, with KI values of <100 nM against hCA IX. Compound 4 b was the best inhibitor (KI =78.5 nM). All the compounds inhibited hCA XIII in the low-nanomolar to sub-micromolar range, with compound 4 b again showing the best inhibition (KI =76.3 nM). With compound 4 b as a lead, more-selective inhibitors of hCA IX and hCA XIII or dual hCA IX/XIII inhibitors might be developed.