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Bioorg Med Chem Lett. 2010 Dec 15;20(24):7255-8. doi: 10.1016/j.bmcl.2010.10.094. Epub 2010 Oct 25.

7,8-disubstituted- but not 6,7-disubstituted coumarins selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the cytosolic ones I and II in the low nanomolar/subnanomolar range.

Author information

1
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Sesto Fiorentino (Firenze), Italy.

Abstract

Two series of disubstituted coumarins incorporating ether and acetyl/propionyl moieties in positions 6,7- and 7,8- of the heterocyclic ring were synthesized investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). All these coumarins were very weak or ineffective as inhibitors of the housekeeping, offtarget isoforms CA I and II. The 6,7-disubstituted series showed ineffective inhibition also for the transmembrane tumor-associated isoforms CA IX and XII, whereas the corresponding isomeric 7,8-disubstituted coumarins showed nanomolar/subnanomolar inhibition of CA IX/XII. The nature and position of the groups substituting the coumarin ring in the 7,8-positions greatly influenced CA inhibitory properties, with C1-C4 alkyl ethers being the most effective inhibitors.

PMID:
21067924
DOI:
10.1016/j.bmcl.2010.10.094
[Indexed for MEDLINE]

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