INHIBITORY ACTIVITY AND MECHANISM OF INHIBITION OF THE N-[[(4-BENZOYLAMINO)PHENYL]SULFONYL]AMINO ACID ALDOSE REDUCTASE INHIBITORS

被引:9
作者
DERUITER, J
MAYFIELD, CA
机构
[1] Department of Pharmacal Sciences, School of Pharmacy, Auburn University
关键词
D O I
10.1016/0006-2952(90)90715-W
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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). © 1990.
引用
收藏
页码:2219 / 2226
页数:8
相关论文
共 22 条
[1]   ANTICONVULSANT ACTION OF ETHANOLAMINE-O-SULFATE AND DI-NORMAL-PROPYLACETATE AND METABOLISM OF GAMMA-AMINOBUTYRIC ACID (GABA) IN MICE WITH AUDIOGENIC-SEIZURES [J].
ANLEZARK, G ;
HORTON, RW ;
MELDRUM, BS ;
CHRISTINA, M ;
SAWAYA, B .
BIOCHEMICAL PHARMACOLOGY, 1976, 25 (04) :413-417
[2]  
BARLOW RB, 1983, BIODATA HANDLING MIC
[3]   GLOMERULAR POLYOL ACCUMULATION IN DIABETES AND ITS PREVENTION BY ORAL SORBINIL [J].
BEYERMEARS, A ;
KU, L ;
COHEN, MP .
DIABETES, 1984, 33 (06) :604-607
[4]  
CARLBERG I, 1985, METHOD ENZYMOL, V113, P484
[5]   SYNTHESIS AND LIQUID-CHROMATOGRAPHIC EVALUATION OF SOME CHIRAL DERIVATIZING AGENTS FOR RESOLUTION OF AMINE ENANTIOMERS [J].
CLARK, CR ;
BARKSDALE, JM .
ANALYTICAL CHEMISTRY, 1984, 56 (06) :958-962
[6]   N-SUBSTITUTED AND 2-SUBSTITUTED N-(PHENYLSULFONYL)GLYCINES AS INHIBITORS OF RAT LENS ALDOSE REDUCTASE [J].
DERUITER, J ;
BORNE, RF ;
MAYFIELD, CA .
JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (01) :145-151
[7]   INVITRO ALDOSE REDUCTASE INHIBITORY ACTIVITY OF SUBSTITUTED N-BENZENESULFONYLGLYCINE DERIVATIVES [J].
DERUITER, J ;
BRUBAKER, AN ;
GARNER, MA ;
BARKSDALE, JM ;
MAYFIELD, CA .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1987, 76 (02) :149-152
[8]  
DVORNIK D, 1987, ALDOSE REDUCTASE INH
[9]  
EICHNER RD, 1982, METHOD ENZYMOL, V89, P359
[10]  
GREENE DA, 1987, NEW ENGL J MED, V316, P599