Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug sulthiame with twelve mammalian isoforms: Kinetic and X-ray crystallographic studies

被引：27

作者：

Temperini, Claudia

Innocenti, Alessio

Mastrolorenzo, Antonio

Scozzafava, Andrea

Supuran, Claudiu T.

机构：

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

[2] Univ Florence, Dipartimento Sci Dermatol, Ctr MTS, I-50121 Florence, Italy

来源：

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

关键词：

carbonic anhydrase; sulthiame; sultam; x-ray crystallography; antiepileptic; sulfonamide; sulfamate;

D O I：

10.1016/j.bmcl.2007.06.044

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Sulthiame, a clinically used antiepileptic, was investigated for its interaction with 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2. 1. 1) isoforms. The drug is a potent inhibitor of CA 11, VII, IX, and X11 (K-1S of 6-56 nM), and a medium potency inhibitor against CA IV, VA, VB, and VI (K-1S of 81-134 nM). The high resolution crystal structure of the hCA II-sulthiame adduct revealed a large number of favorable interactions between the drug and the enzyme which explain its strong low nanomolar affinity for this isoform and may also be exploited for the design of effective inhibitors incorporating sultam moieties. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：4866 / 4872

页数：7

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