Synthesis and biological evaluation of a new family of anti-benzylanilinosulfonamides as CA IX inhibitors.

Abstract

We report the synthesis and the pharmacological evaluation of a new class of human carbonic anhydrase (hCA) inhibitors prepared regio- and stereoselectively by reacting sulfanilamide with ethyl trans-phenylglycidate in the presence of cobalt(II) chloride. Various derivatizations of the ester moiety in the parent compound led to a small library of derivatives (2R,3R and 2S,3S) which displayed interesting inhibitory activities towards the human tumor-associated isoform CA IX. One of the new compounds shows high selectivity in inhibiting hCA IX compared to the two physiologically relevant, cytosolic isozymes hCA I and hCA II. A molecular modeling study was conducted in order to simulate the binding mode of this new family of enzyme inhibitors within the active sites of hCA IX and hCA II.

• Authors: Anne Thiry, Aurélie Delayen, Laurence Goossens, Raymond Houssin, Marie Ledecq, Aurélie Frankart, Jean-Michel Dogné, Johan Wouters, Claudiu T Supuran, Jean-Pierre Hénichart, Bernard Masereel
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 44 Issue 2 Pg. 511-8 (Feb 2009) ISSN: 1768-3254 [Electronic] France
• PMID: 18479784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Carbonic Anhydrase Inhibitors
• Sulfanilamides
• Sulfonamides
• Sulfanilamide
• CA9 protein, human
• Carbonic Anhydrase IX
• Carbonic Anhydrases

Topics

• Antigens, Neoplasm (drug effects)
• Binding Sites
• Carbonic Anhydrase IX
• Carbonic Anhydrase Inhibitors (chemical synthesis)
• Carbonic Anhydrases (drug effects)
• Humans
• Models, Molecular
• Protein Binding
• Structure-Activity Relationship
• Sulfanilamide
• Sulfanilamides
• Sulfonamides (chemical synthesis, pharmacology)