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

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

doi:10.1016/j.ejmech.2008.03.034

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

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

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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.

Original language	English
Pages (from-to)	511-8
Number of pages	8
Journal	European Journal of Medicinal Chemistry
Volume	44
Issue number	2
DOIs	https://doi.org/10.1016/j.ejmech.2008.03.034
Publication status	Published - 1 Feb 2009

Keywords

Carbonic anhydrase
Molecular modeling
Sulfonamide
Tumor-associated isoform

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10.1016/j.ejmech.2008.03.034

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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.",

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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

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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 -

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

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Keywords

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