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Inhibitory effect of quinolone antimicrobial and nonsteroidal anti-inflammatory drugs on a medium chain acyl-CoA synthetase11Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; NQs, quinolone antimicrobial drugs; DTT, dithiothreitol; and GABA, γ-aminobutyric acid

Authors :
Yuichi Kawai
Masato Hiasa
Fumiyo Kasuya
Kazuo Igarashi
Miyoshi Fukui
Source :
Biochemical Pharmacology. 62:363-367
Publication Year :
2001
Publisher :
Elsevier BV, 2001.

Abstract

The inhibitory effects of quinolone antimicrobial agents and nonsteroidal anti-inflammatory drugs on purified mouse liver mitochondrial medium chain acyl-CoA synthetase catalyzing the first reaction of glycine conjugation were examined, using hexanoic acid as a substrate. Enoxacin, ofloxacin, nalidixic acid, diflunisal, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid, which do not act as substrates, were potent inhibitors. Diflunisal, nalidixic acid, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid inhibited competitively this medium chain acyl-CoA synthetase with K(i) values of 0.6, 12.4, 19.6, 13.4, and 15.0 microM, respectively. Enoxacin and ofloxacin inhibited this medium chain acyl-CoA synthetase in a mixed-type manner with K(i) values of 23.7 and 38.2 microM, respectively. Felbinac, which is a substrate, inhibited the activity of this medium chain acyl-CoA synthetase for hexanoic acid (IC50 = 25 microM). The concomitant presence of enoxacin and felbinac strongly inhibited this medium chain acyl-CoA synthetase. These findings indicate that medium chain acyl-CoA synthetases may be influenced by quinolone antimicrobial and nonsteroidal anti-inflammatory drugs.

Details

ISSN :
00062952
Volume :
62
Database :
OpenAIRE
Journal :
Biochemical Pharmacology
Accession number :
edsair.doi...........c7d253c3c36c3d63295b79d6d98d6083
Full Text :
https://doi.org/10.1016/s0006-2952(01)00667-0