期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 15, 期 13, 页码 3302-3306出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2005.04.058
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A library of boron-containing carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, including sulfonamides, sulfamides, and sulfamates is reported. The new compounds have been synthesized by derivatization reactions of 4-carboxy-/amino-/hydroxy-phenylboronic acid pinacol esters with amino/isothiocyanato-substituted aromatic/heteroaromatic sulfonamides or by sulfamoylation reactions with sulfamoyl chloride. The new derivatives have been assayed for the inhibition of three physiologically relevant CA isozymes, the cytosolic CA I and II, and the transmembrane, tumor-associated isozyme CA IX. Effective inhibitors were detected both among sulfonamides, sulfamates, and sulfamides. Against the human isozyme hCA I the new compounds showed inhibition constants in the range of 34-94 nM, against hCA II in the range of 3.1-48 nM, and against hCA IX in the range of 7.3-89 nM, respectively. As hypoxic tumors highly overexpress CA IX, the design of boron-containing inhibitors with high affinity for the tumor-associated CA isozymes may lead to important advances in boron neutron capture therapy (BNCT) applications targeting such tumors, which are non-responsive to both classical chemo- and radiotherapy. (c) 2005 Elsevier Ltd. All rights reserved.
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