Ureido-substituted sulfamates show potent carbonic anhydrase IX inhibitory and antiproliferative activities against breast cancer cell lines.

Abstract

A series of 50 sulfamates were obtained by reacting 4-aminophenol with isocyanates followed by sulfamoylation. Most of the new compounds were nanomolar inhibitors of the tumor-associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms IX and XII, whereas they inhibited less cytosolic offtarget isoforms CA I and II. Some of these sulfamates showed significant antiproliferative activity in several breast cancer cell lines, such as SKBR3, MCF10A, ZR75/1, MDA-MB-361 and MCF7, constituting interesting anticancer leads.

• Authors: Jean-Yves Winum, Fabrizio Carta, Carol Ward, Peter Mullen, David Harrison, Simon P Langdon, Alessandro Cecchi, Andrea Scozzafava, Ian Kunkler, Claudiu T Supuran
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 14 Pg. 4681-5 (Jul 15 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22721713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Carbonic Anhydrase Inhibitors
• Sulfonic Acids
• sulfamic acid
• Carbonic Anhydrases

Topics

• Breast Neoplasms (drug therapy, enzymology, pathology)
• Carbonic Anhydrase Inhibitors (chemistry, pharmacology)
• Carbonic Anhydrases (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Molecular Structure
• Structure-Activity Relationship
• Sulfonic Acids (chemistry, pharmacology)