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

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4681-5. doi: 10.1016/j.bmcl.2012.05.083. Epub 2012 May 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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