Carbonic anhydrase inhibitors. Inhibition of the cytosolic human isozymes I and II, and the transmembrane, tumor-associated isozymes IX and XII with substituted aromatic sulfonamides activatable in hypoxic tumors

被引：44

作者：

Saczewski, Franciszek

Slawinski, Jaroslaw

Kornicka, Anita

Brzozowski, Zdzislaw

Pomarnacka, Elzbieta

Innocenti, Alessio

Scozzafava, Andrea

Supuran, Claudiu T.

机构：

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

[2] Med Univ Gdansk, Dept Chem Technol Drugs, PL-80416 Gdansk, Poland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 18期

关键词：

carbonic anhydrase; sulfonamides; disulfides; hypoxia; prodrug; tumor;

D O I：

10.1016/j.bmcl.2006.06.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Some 2-mercapto-substituted-benzenesulfonamides and their disulfides/sulfones were prepared and investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is, CA I and II (cytosolic enzymes), and the tumor-associated CA IX and XII. Some mercaptans led to a consistent increase of inhibitory power (52.8- to 243-fold) over the corresponding oxidized (S-S type) derivatives, acting as potential hypoxia-activatable drugs. (c) 2006 Elsevier Ltd. All rights reserved.

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收藏

页码：4846 / 4851

页数：6

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