Sulfonamides incorporating boroxazolidone moieties are potent inhibitors of the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII

Marouan Rami; Alfonso Maresca; Fatma-Zhora Smaine; Jean-Louis Montero; Andrea Scozzafava; Jean-Yves Winum; Claudiu T Supuran

doi:10.1016/j.bmcl.2011.03.055

Sulfonamides incorporating boroxazolidone moieties are potent inhibitors of the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII

Bioorg Med Chem Lett. 2011 May 15;21(10):2975-9. doi: 10.1016/j.bmcl.2011.03.055. Epub 2011 Mar 21.

Authors

Marouan Rami¹, Alfonso Maresca, Fatma-Zhora Smaine, Jean-Louis Montero, Andrea Scozzafava, Jean-Yves Winum, Claudiu T Supuran

Affiliation

¹ Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.

PMID: 21470859
DOI: 10.1016/j.bmcl.2011.03.055

Abstract

A new series of sulfonamides was synthesized by the reaction of the boroxazolidone complex of l-lysine with isothiocyanates incorporating sulfamoyl moieties and diverse organic scaffolds. The obtained thioureas have been investigated as inhibitors of four physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. Inhibition between the low nanomolar to the micromolar range has been observed against them, with several low nanomolar and tumor-CA selective inhibitors detected. These boron-containing compounds might be useful for the management of hypoxic tumors overexpressing hCA IX/XII by means of boron neutron capture therapy, a technique not investigated so far with inhibitors of this enzyme.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Neoplasm / metabolism*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Boron Compounds / chemistry*
Carbonic Anhydrase IX
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Enzyme Activation / drug effects*
Humans
Molecular Structure
Neoplasm Proteins / antagonists & inhibitors
Oxazolidinones / chemistry*
Protein Isoforms
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Antigens, Neoplasm
Antineoplastic Agents
Boron Compounds
Carbonic Anhydrase Inhibitors
Neoplasm Proteins
Oxazolidinones
Protein Isoforms
Sulfonamides
boroxazolidone
CA9 protein, human
Carbonic Anhydrase IX
Carbonic Anhydrases
carbonic anhydrase XII