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

Alessio Innocenti, Mika Hilvo, Andrea Scozzafava, Seppo Parkkila, Claudiu T. Supuran (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

61 Citations (Scopus)

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 μM, whereas compounds incorporating 4-amino-, 4-cyano, or 3-hydroxy groups were less effective (KIs of 335–434 μM). The best phenol inhibitor was clioquinol (KI of 2.33 μM). 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.
Original languageEnglish
Pages (from-to)3593-3596
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number12
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

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