TY - JOUR
T1 - Synthesis and biological evaluation of a new family of anti-benzylanilinosulfonamides as CA IX inhibitors
AU - Thiry, Anne
AU - Delayen, Aurélie
AU - Goossens, Laurence
AU - Houssin, Raymond
AU - Ledecq, Marie
AU - Frankart, Aurélie
AU - Dogné, Jean-Michel
AU - Wouters, Johan
AU - Supuran, Claudiu T
AU - Hénichart, Jean-Pierre
AU - Masereel, Bernard
PY - 2009/2/1
Y1 - 2009/2/1
N2 - 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.
AB - 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.
KW - Carbonic anhydrase
KW - Molecular modeling
KW - Sulfonamide
KW - Tumor-associated isoform
UR - http://www.scopus.com/inward/record.url?scp=60149101971&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2008.03.034
DO - 10.1016/j.ejmech.2008.03.034
M3 - Article
C2 - 18479784
SN - 0223-5234
VL - 44
SP - 511
EP - 518
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 2
ER -