Carbonic anhydrase inhibitors: Aliphatic N-phosphorylated sulfamates - A novel zinc-anchoring group leading to nanomolar inhibitors

Laurent Bonnac, Alessio Innocent, Jean Yves Winum, Angela Casini, Jean Louis Montero, Andrea Scozzafava, Veronique Barragan, Claudiu T. Supuran

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)275-278
Number of pages4
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume19
Issue number3
DOIs
StatePublished - Jun 2004
Externally publishedYes

Bibliographical note

Funding 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.

Keywords

  • Carbonic anhydrase
  • Isozyme I, II
  • N-phosphorylated sulfamate
  • Sulfamate

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