A small library of phosphorylated sulfamates (N-(O-alkylsulfamoyl)-phosphoramidic acids) incorporating long aliphatic chains (C8-C16) has been synthesized and investigated for their interaction with two physiologically relevant carbonic anhydrase (CA) isozymes. These compounds behaved as very potent inhibitors of both isozymes, with inhibition constants in the range of 8.2-16.1 nM against isozyme hCA I, and 5.3-11.9 nM against isozyme hCA II. Activity was optimal for the n-octyl derivative (similarly with that of the corresponding unsubstituted sulfamates) and gradually decreased for the longer chain derivatives. Some of these compounds are much more effective CA inhibitors as compared to the clinically used derivatives acetazolamide, sulfanilamide or topiramate, which are used as standards for the enzymatic determinations. The phosphorylated sulfamate moiety represents a novel zinc-binding group for the design of effective CA inhibitors.
|Number of pages
|Journal of Enzyme Inhibition and Medicinal Chemistry
|Published - Jun 2004
Bibliographical noteFunding Information:
Financial support for this work from La Ligue contre le Cancer (Comité de l’Aude et du Gard - France) (for L.B., Ph.D fellowship) is gratefully acknowledged.
- Carbonic anhydrase
- Isozyme I, II
- N-phosphorylated sulfamate