N-β-glycosyl sulfamides are selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII

Bioorg Med Chem Lett. 2011 Aug 1;21(15):4447-50. doi: 10.1016/j.bmcl.2011.06.031. Epub 2011 Jun 16.

Abstract

The transmembrane isoforms of carbonic anhydrase (CA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this Letter, we present a series of peracetylated and deprotected N-β-glycosyl sulfamides that were tested for the inhibition of 4 carbonic anhydrase isoforms: the cytosolic hCA I and hCA II and transmembrane tumor-associated IX and XII. Compounds 1-4 and 6-8 selectively target cancer-associated CAs (IX and XII) with K(I)s in the low nanomolar range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology
  • Antigens, Neoplasm / chemistry*
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Carbonic Anhydrase I / antagonists & inhibitors
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase II / antagonists & inhibitors
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase IX
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / metabolism
  • Humans
  • Neoplasms / enzymology
  • Structure-Activity Relationship

Substances

  • Amides
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases
  • carbonic anhydrase XII