Prooxidant toxicity of polyphenolic antioxidants to HL-60 cells: description of quantitative structure-activity relationships

Citation
E. Sergediene et al., Prooxidant toxicity of polyphenolic antioxidants to HL-60 cells: description of quantitative structure-activity relationships, FEBS LETTER, 462(3), 1999, pp. 392-396
Citations number
30
Categorie Soggetti
Biochemistry & Biophysics
Journal title
FEBS LETTERS
ISSN journal
00145793 → ACNP
Volume
462
Issue
3
Year of publication
1999
Pages
392 - 396
Database
ISI
SICI code
0014-5793(199912)462:3<392:PTOPAT>2.0.ZU;2-3
Abstract
Polyphenolic antioxidants exhibited a dose-dependent toxicity against human promyelocytic leukemia cells (HL-60). Their action was accompanied by malo ndialdehyde formation, and was partly prevented by desferrioxamine and the antioxidant N,N'-diphenyl-p-phenylene diamine, This points to a prooxidant character of their cytotoxicity. A quantitative structure-activity relation ship (QSAR) has been obtained to describe the cytotoxicity of 13 polyphenol ic antioxidants belonging to three different groups (flavonoids, derivative s of gallic and caffeic acid): log cL(50) (mu M) = (2.7829 +/- 0.2339)+(1.2 734 +/- 0.4715) E-p/2 (V)-(0.3438 +/- 0.0582) log P (r(2) = 0.8129), where cL(50) represents the concentration for 50% cell survival, E-p/2 represents the voltammetric midpoint potential, and P represents the octanol/water pa rtition coefficient, Analogous QSARs were obtained using enthalpies of sing le-electron oxidation of these compounds, obtained by quantum-mechanical ca lculations, These findings clearly point to two important characteristics d etermining polyphenol cytotoxicity, namely their ease of oxidation and thei r Lipophilicity. (C) 1999 Federation of European Biochemical Societies.