Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 15, Issue 6, Pages 2298-2311Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2007.01.023
Keywords
carbonic anhydrase inhibitors; matrix metalloproteinase inhibitors; hydroxamic acid inhibitors
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A series of sulfonylated hydroxamates were synthesized and evaluated as dual inhibitors of both human carbonic anhydrases (hCAs) and matrix metalloproteinases (MMPs), two metalloenzyme families involved in carcinogenesis and tumor invasion processes. The new derivatives were tested on three CA isozymes, the cytosolic isozymes I and II, and the transmembrane, tumor-associated isozyme IX, and also on human gelatinases (MMP-2 and MMP-9). Some of the new derivatives proved to be potent and selective inhibitors of CA II, but only compounds 3b and 6b, devoid of the arylsulfonyl moiety, proved to have a better inhibitory activity on hCA IX than on hCA I and II, in the micromolar range. (c) 2007 Elsevier Ltd. All rights reserved.
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