Synthesis and in vitro studies of pyrone derivatives as scavengers of active oxygen species.
The antioxidant properties of eleven alpha-pyrones and four gamma-pyrones were evaluated by means of three different tests: reduction of the stable free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion scavenging assay and lipid peroxidation assay. In the DPPH test, 6-aryl-5,6-dihydro-4-hydroxypyran-2-ones (3) and 4-hydroxypyran-2-one (5f) were the most active derivatives with IC50 values ranging from 36.7 to 394 mumol/l. Potent superoxide anion scavenging properties appeared in derivatives possessing phenol moieties. Thus phenolic pyrones 5e and 5f exhibited a noteworthy activity (IC50 = 0.180 and 0.488 mmol/l, respectively) when reference compound, ascorbic acid, demonstrated only 24% inhibition at a concentration of 1 mg/ml. In addition derivative 5f significantly inhibited the Fe2+/ADP/ascorbate-induced lipid peroxidation of rat liver microsomes with an IC50 value of 0.069 mmol/l. Due to its multiple mechanism of protective action, compound 5f may be useful for the treatment of oxidative tissue injury in human disease.
Weber
V
V
Laboratoire de Chimie Thérapeutique-Groupe de Recherche en Pharmacochimie, Clermont-Ferrand, France.
Coudert
P
P
Duroux
E
E
Leal
F
F
Couquelet
J
J
Madesclaire
M
M
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D015764:Bepridil / Q000031:analogs & derivatives* / Q000494:pharmacology; D001713:Biphenyl Compounds; D005609:Free Radicals / Q000737:chemistry; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010851:Picrates; D011753:Pyrones / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000737:chemistry
D000975:Antioxidants; D001713:Biphenyl Compounds; D005609:Free Radicals; D007202:Indicators and Reagents; D010851:Picrates; D011753:Pyrones; D017382:Reactive Oxygen Species; D013481:Superoxides; D015764:Bepridil; C004931:1,1-diphenyl-2-picrylhydrazyl