Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII.

A series of 6-ureido/amidocoumarins ( and ) has been designed and synthesised to develop potent and isoform- selective carbonic anhydrase CA XI and XII inhibitors. All coumarin derivatives were investigated for their CA inhibitory effect against CA I, II, IX, and XII. Interestingly, target coumarins potently inhibited both tumour-related isoforms CA IX (s: 14.7-82.4 nM) and CA XII (s: 5.9-95.1 nM), whereas the cytosolic off-target CA I and II isoforms have not inhibited by all tested coumarins up to 100 μM. These findings granted the target coumarins an excellent selectivity profile towards both CA IX and CA XII isoforms, supporting their development as promising anticancer candidates. Moreover, all target molecules were evaluated for their anticancer activities against HCT-116 and MCF-7 cancer cells. The 3,5-bis-trifluoromethylphenyl ureidocoumarin , exerted the best anticancer activity. Overall, ureidocoumarins, particularly compound could serve as a promising prototype for the development of potent anticancer CAIs.