title: 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.affiliation: Drug Design and Discovery Center, FUNDP, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium. anne.thiry@fundp.ac.be
authors.forename: Anne
authors.initials: A
authors.lastname: Thiry
authors.forename: Aurélie
authors.initials: A
authors.lastname: Delayen
authors.forename: Laurence
authors.initials: L
authors.lastname: Goossens
authors.forename: Raymond
authors.initials: R
authors.lastname: Houssin
authors.forename: Marie
authors.initials: M
authors.lastname: Ledecq
authors.forename: Aurélie
authors.initials: A
authors.lastname: Frankart
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
authors.forename: Johan
authors.initials: J
authors.lastname: Wouters
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hénichart
authors.forename: Bernard
authors.initials: B
authors.lastname: Masereel
mesh_terms: D000951:Antigens, Neoplasm / Q000187:drug effects*; D001665:Binding Sites; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis*; D002256:Carbonic Anhydrases / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship; D000077145:Sulfanilamide; D013424:Sulfanilamides; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; D013424:Sulfanilamides; D013449:Sulfonamides; D000077145:Sulfanilamide; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases