期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 23, 期 7, 页码 1430-1436出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2015.02.023
关键词
Carbonic anhydrase; Inhibitor; Sulfocoumarin; Tumor-associated enzyme
资金
- Marie Curie ITN FP7 project (Dynano)
A series of 6-aryl-substituted 1,2-benzoxathiine 2,2-dioxides was obtained by reacting 6-iodo-sulfo-coumarin with arylboronic acids in Suzuki cross-coupling conditions. The new sulfocoumarins incorporating various substituted phenyl moieties in position 6 of the heterocyclic ring were investigated for the inhibition of four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms with medicinal chemistry applications, the cytosolic hCA I and II, and the transmembrane, tumor-associated hCA IX and XII. The aryl-substituted sulfocoumarins did not inhibit the ubiquitous, off-target cytosolic isoforms hCA I and II (K(I)s > 10 mu M) but showed effective inhibition against the two transmembrane CAs, with K(I)s ranging from 9.0 to 95.3 nM against hCA IX, and between 3.5 and 14.2 nM against hCA XII. As hCA IX and XII are validated anti-tumor targets, such sulfocoumarin, isoform-selective inhibitors may be useful for identifying suitable drug candidates for further clinical trials of this class of pharmacologic agents. (C) 2015 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据