Synthesis and biological activities of aldose reductase inhibitors bearing acyl benzenesulfonamides as carboxylic acid surrogates

Isaac O. Donkor, Yasser S. Abdel-Ghany, Peter F. Kador, Tadashi Mizoguchi, Anita Bartoszko-Malik, Duane D. Miller

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We have synthesized alrestatin derivatives 1-11 possessing acyl benzenesulfonamide groups as surrogates for the carboxylic acid moiety of alrestatin. Most of the compounds were inactive as aldose reductase inhibitors compared to alrestatin, however, some of them demonstrated selectivity towards inhibition of rat kidney aldehyde reductase compared to rat lens aldose reductase suggesting that structural differences may exist between the carboxylic acid binding domains of these closely related enzymes. The chemoreactive derivatives 9 and l0 suggested the presence of a nucleophile(s) at the carboxylic acid binding site on aldose reductase.

Original languageEnglish (US)
Pages (from-to)15-22
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume33
Issue number1
DOIs
StatePublished - Jan 1998

Fingerprint

Bearings (structural)
Aldehyde Reductase
Carboxylic Acids
Bioactivity
Rats
Derivatives
Nucleophiles
Lenses
Binding Sites
Kidney
benzenesulfonamide
Enzymes
alrestatin

Keywords

  • Acyl benzenesulfonamide
  • Aldose reductase inhibitor
  • Alrestatin
  • Carboxylic acid surrogate
  • Diabetic complication

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Synthesis and biological activities of aldose reductase inhibitors bearing acyl benzenesulfonamides as carboxylic acid surrogates. / Donkor, Isaac O.; Abdel-Ghany, Yasser S.; Kador, Peter F.; Mizoguchi, Tadashi; Bartoszko-Malik, Anita; Miller, Duane D.

In: European Journal of Medicinal Chemistry, Vol. 33, No. 1, 01.1998, p. 15-22.

Research output: Contribution to journalArticle

Donkor, Isaac O. ; Abdel-Ghany, Yasser S. ; Kador, Peter F. ; Mizoguchi, Tadashi ; Bartoszko-Malik, Anita ; Miller, Duane D. / Synthesis and biological activities of aldose reductase inhibitors bearing acyl benzenesulfonamides as carboxylic acid surrogates. In: European Journal of Medicinal Chemistry. 1998 ; Vol. 33, No. 1. pp. 15-22.
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