Carbonic anhydrase inhibitors:: The β-carbonic anhydrase from Helicobacter pylori is a new target for sulfonamide and sulfamate inhibitors

被引：141

作者：

Nishimori, Isao

Minakuchi, Tomoko

Kohsaki, Takuhiro

Onishi, Saburo

Takeuchi, Hiroaki

Vullo, Daniela

Scozzafava, Andrea

Supuran, Claudiu T.

机构：

[1] Univ Florence, Chim Bioorgan Lab, I-50019 Florence, Italy

[2] Kochi Med Sch, Dept Lab Med, Kochi 7838505, Japan

[3] Kochi Med Sch, Dept Gastroenterol & Hepatol, Kochi 7838505, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 13期

关键词：

MESSENGER-RNA EXPRESSION; MITOCHONDRIAL ISOZYME-V; CRYSTAL-STRUCTURE; ACTIVE-SITE; QUADRUPLE THERAPY; TRIPLE THERAPY; CDNA CLONING; CO2; ALGA; TRANSMEMBRANE;

D O I：

10.1016/j.bmcl.2007.04.063

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

DNA clones for the P-class carbonic anhydrase (CA, EC 4.2.1.1) of Helicobactor pylori (hp beta CA) were obtained. A recombinant hp beta CA protein lacking the N-terminal 15-arnino acid residues was produced and purified, representing a catalytically efficient CA. hp beta CA was strongly inhibited (K(1)s in the range of 24-45 nM) by many sulfonamides/sulfamates, among which acetazolamide, ethoxzolamide, topiramate, and sulpiride, all clinically used drugs. The dual inhibition of alpha- and/or beta-class CAs of H. pylori might represent a useful alternative for the management of gastritis/gastric ulcers, as well as gastric cancer. This is also the first study showing that a bacterial beta-CA can be a drug target. (c) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：3585 / 3594

页数：10

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