Carbonic anhydrase inhibitors: Inhibition of the new membrane-associated isoform XV with phenols.

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Innocenti A, Hilvo M, Scozzafava A, Parkkila S, Supuran CT

Carbonic anhydrase inhibitors: Inhibition of the new membrane-associated isoform XV with phenols.

Bioorg Med Chem Lett. 2008 Jun 15;18(12):3593-6. doi: 10.1016/j.bmcl.2008.04.077. Epub 2008 May 4.

PubMed ID

18501600 [ View in PubMed

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Abstract

Inhibition of the newest isoform of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), CA XV, with a series of phenols was investigated. Murine CA XV showed an inhibition profile by phenols distinct of those of the cytosolic human isoforms CA I and II. Phenol and some of its 2-, 3-, and 4-substituted derivatives incorporating hydroxy, fluoro, carboxy, and acetamido moieties were effective CA XV inhibitors, with inhibition constants in the range of 7.20-11.30 microM, whereas compounds incorporating 4-amino-, 4-cyano, or 3-hydroxy groups were less effective (K(I)s of 335-434 microM). The best phenol inhibitor was clioquinol (K(I) of 2.33 microM). Phenols show a different inhibition mechanism as compared to sulfonamides and their isosteres, and may lead to the design of compounds with selectivity for inhibiting different CA isozymes with medicinal chemistry applications.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Acetazolamide	Carbonic anhydrase 1	Ki (nM)	250	N/A	N/A	Details
Acetazolamide	Carbonic anhydrase 2	Ki (nM)	12	N/A	N/A	Details