The α and β Classes Carbonic Anhydrases from Helicobacter pylori as Novel Drug Targets

Authors: Nishimori, Isao1; Onishi, Saburo1; Takeuchi, Hiroaki1; Supuran, Claudiu T.1

Source: Current Pharmaceutical Design, Volume 14, Number 7, March 2008 , pp. 622-630(9)

Publisher: Bentham Science Publishers

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Abstract:

Helicobacter pylori (H. pylori) successfully resides in the human stomach in highly acidic conditions, causing a variety of gastroduodenal lesions, including gastric ulcer, gastric cancer and MALT lymphoma. For acid acclimation of H. pylori, two types of enzymes, urease and carbonic anhydrase (CA), play a central role. They cooperatively function to maintain neutral pH in the bacterial cytoplasm and periplasm. The genome project of H. pylori identified two different classes of CA with different subcellular localization: a periplasmic α-class CA (hpαCA) and a cytoplasmic β-class CA (hpβCA). These two CAs are catalytically efficient with almost identical activity to that of the human isoform CA I for the CO2 hydration reaction, and highly inhibited by many sulfonamides/sulfamates, including acetazolamide, ethoxzolamide, topiramate and sulpiride, all clinically used drugs. Furthermore, certain CA inhibitors, such as acetazolamide and methazolamide, were shown to inhibit the bacterial growth in vitro. Since the efficacy of eradication therapies currently employed has been decreasing due to drug resistance and side effects of the commonly used drugs, the dual inhibition of α- and/or ß-CAs of H. pylori could be applied as an alternative therapy in patients with H. pylori infection or for the prevention of gastroduodenal diseases provoked by this widespread pathogen.

Keywords: H. pylori; carbonic anhydrase; urease; inhibitor; acetazolamide; methazolamide; gastric acid

Document Type: Research article

DOI: 10.2174/138161208783877875

Affiliations: 1: Department of Gastroenterology and Hepatology, Kochi Medical Schoo, Nankoku, Kochi 783-8505,Japan.

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