Antioxidant properties of novel lipophilic ascorbic acid analogues

Citation
V. Weber et al., Antioxidant properties of novel lipophilic ascorbic acid analogues, J PHARM PHA, 52(5), 2000, pp. 523-530
Citations number
29
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACY AND PHARMACOLOGY
ISSN journal
00223573 → ACNP
Volume
52
Issue
5
Year of publication
2000
Pages
523 - 530
Database
ISI
SICI code
0022-3573(200005)52:5<523:APONLA>2.0.ZU;2-X
Abstract
Structural modifications of ascorbic acid by the introduction of lipophilic moieties has led to derivatives with increased stability against thermal a nd oxidative degradation. Two series of new lipophilic ascorbic analogues w ere synthesized to obtain antioxidants devoid of autooxidant properties: 4- benzoyl-3-hydroxyfuran-2(5H)-ones (3a-j) and 4-acetyl-5-aryl-3,4-dihydrofur an-2(5H)ones (5a-f). These compounds were submitted to three different tests: reduction of the s table free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH); superoxide-anion scavenging assay; and lipid-peroxidation assay. Most compounds interacted w ith DPPH: at a concentration of 5 x 10(-3) M, the reducing activity of 4-be nzoyl derivatives, 3c and 3h, was more than 50%; under the same conditions, the rate of inhibition for 4-acetylbutanolides, 5a and 5f, reached 60.6% a nd 87.3%, respectively; 93.3% inhibition was observed with ascorbic acid. I n the superoxide-anion scavenging assay, at a concentration of 1 mg mL(-1), 4-benzoyl derivatives, 3g and 3i, exhibited a good activity, with IC50 (do se resulting in 50% inhibition) values of 1.45 and 1.35 x 10(-3) M, respect ively. 4-Acetylbutanolide 5f, significantly inhibited the Fe2+/ADP/ascorbat e-induced lipid peroxidation of rat liver microsomes with an IC50 of 4.9 x 10(-4) M. This study demonstrates that enol functions in the structure of ascorbic ac id analogues are not absolutely essential to bring about antioxidant effect s.