Inhibitory effect of quinolone antimicrobial and nonsteroidal anti-inflammatory drugs on a medium chain acyl-CoA synthetase

Kasuya, F Hiasa, M Kawai, Y Igarashi, K Fukui, M

F. Kasuya et al., Inhibitory effect of quinolone antimicrobial and nonsteroidal anti-inflammatory drugs on a medium chain acyl-CoA synthetase, BIOCH PHARM, 62(3), 2001, pp. 363-367

20

INGLESE

Article

Pharmacology & Toxicology

BIOCHEMICAL PHARMACOLOGY

0006-2952 → ACNP

62

3

2001

363 - 367

ISI

0006-2952(20010801)62:3<363:IEOQAA>2.0.ZU;2-U

The inhibitory effects of quinolone antimicrobial agents and nonsteroidal a nti-inflammatory drugs on purified mouse liver mitochondrial medium chain a cyl-CoA synthetase catalyzing the first reaction of glycine conjugation wer e examined, using hexanoic acid as a substrate. Enoxacin, ofloxacin, nalidi xic acid, diflunisal, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydrox ydodecanoic acid, which do not act as substrates, were potent inhibitors. D iflunisal, nalidixic acid, salicylic acid, 2-hydroxynaphthoic acid, and 2-h ydroxydodecanoic acid inhibited competitively this medium chain acyl-CoA sy nthetase with K-i values of 0.6, 12.4, 19.6, 13.4, and 15.0 muM, respective ly. 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 muM, respectively. Felbinac, which is a substrate, inhibited the activity of this medium chain acyl-CoA synthetase for hexanoic acid (IC50 = 25 muM). The concomitant pre sence of enoxacin and felbinac strongly inhibited this medium chain acyl-Co A synthetase. These findings indicate that medium chain acyl-CoA synthetase s may be influenced by quinolone antimicrobial and nonsteroidal anti-inflam matory drugs. (C) 2001 Elsevier Science Inc. All rights reserved.