Coumarins incorporating hydroxy- and chloro-moieties selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the cytosolic ones I and II

Add time:08/22/2019    Source:sciencedirect.com

A series of coumarins incorporating hydroxy-, chloro- and/or chloromethyl-moieties in positions 3-, 4-, 6- and 7- of the heterocyclic ring were investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). These coumarins were very weak or ineffective as inhibitors of the house-keeping, offtarget isoforms CA I and II, but showed effective, submicromolar inhibition of the transmembrane, tumor-associated isoforms CA IX and XII. The nature and position of the groups substituting the coumarin ring greatly influenced CA inhibitory properties. 6-Hydroxycoumarin showed KIs >100 μM against CA I and II, of 0.198 μM against CA IX and of 0.683 μM against CA XII, being thus a selective, efficient inhibitor for the tumor-associated over cytosolic isoforms. These compounds are also excellent leads for designing isoform-selective enzyme inhibitors.

We also recommend Trading Suppliers and Manufacturers of 6-CHLORO-4-HYDROXYCOUMARIN (cas 19484-57-2). Pls Click Website Link as below: cas 19484-57-2 suppliers

Prev:Hydroxycoumarins as selective MAO-B inhibitors
Next:Synthesis of new5-alkylidene-4-chloro-5H-1,2,3-dithiazoles and their stereochemistry)