Inhibitory activity and mechanism of inhibition of the N-[[(4-benzoylamino)phenyl]sulfonyl]amino acid aldose reductase inhibitors

Biochemical Pharmacology
J DeRuiter, C A Mayfield

Abstract

A series of substituted N-[[(4-benzoylamino)phenyl]sulfonyl]amino acids (BAPS-amino acids) were synthesized by established methods, and the stereochemistry of the products was confirmed by HPLC analysis after chiral derivatization. When tested against aldose reductase (alditol:NADP+ oxidoreductase; EC 1.1.1.21; ALR2) isolated from rat lens, all of the BAPS-amino acids were determined to be significantly more inhibitory than the corresponding N-(phenylsulfonyl)amino acids. Structure-inhibition and enzyme kinetic analyses suggest that the BAPS-amino acids inhibit ALR2 by a mechanism similar to the N-(phenylsulfonyl)amino acids. However, multiple inhibition analyses indicate that the increased inhibitory activity of the BAPS-amino acids is a result of interaction with multiple sites present on ALR2. Enzyme specificity studies with several of the BAPS-amino acids demonstrated that these compounds do not produce significant inhibition of other nucleotide-requiring enzymes including aldehyde reductase (alcohol: NADP+ oxidoreductase; EC 1.1.1.2; ALR1).

References

Jan 1, 1989·The International Journal of Biochemistry·C A Mayfield, J DeRuiter
Mar 5, 1987·The New England Journal of Medicine·D A GreeneA A Sima
Mar 1, 1987·Current Eye Research·R Poulsom
Sep 1, 1987·Journal of Medicinal Chemistry·C A Mayfield, J DeRuiter
Jul 1, 1988·Medicinal Research Reviews·P F Kador
Dec 1, 1982·Biochemical Pharmacology·J OkudaM Nakayama

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Citations

Mar 29, 2014·Journal of Enzyme Inhibition and Medicinal Chemistry·Ivana MilackovaMilan Stefek

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