Carbonic anhydrase inhibitors; fluorinated phenyl sulfamates show strong inhibitory activity and selectivity for the inhibition of the tumor-associated isozymes IX and XII over the cytosolic ones I and II.
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| Abstract |
A series of fluorinated-phenylsulfamates have been prepared by sulfamoylation of the corresponding phenols and the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isozymes, the cytosolic CA I and II (off-targets), and the transmembrane, tumor-associated CA IX and XII is investigated. Unlike the lead molecule (phenylsulfamate), a very potent CA I and II inhibitor and a modest CA IX/XII inhibitor, the fluorinated sulfamates were stronger inhibitors of CA IX (K(I)s of 2.8-47 nM) and CA XII (K(I)s of 1.9-35 nM) than of CA I (K(I)s of 53-415 nM) and CA II (K(I)s of 20-113 nM). Some of these compounds were selective CA IX over CA II inhibitors, with selectivity ratios in the range of 11.4-12.1, making them interesting candidates for targeting hypoxic tumors overexpressing CA IX and/or XII.
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| Authors | Jean-Yves Winum, Alessio Innocenti, Daniela Vullo, Jean-Louis Montero, Claudiu T Supuran |
| Journal | Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 17 Pg. 5082-5 (Sep 01 2009) ISSN: 1464-3405 [Electronic] England |
| PMID | 19632111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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