Prooxidant toxicity of polyphenolic antioxidants to HL-60 cells: description of quantitative structure-activity relationships.
Polyphenolic antioxidants exhibited a dose-dependent toxicity against human promyelocytic leukemia cells (HL-60). Their action was accompanied by malondialdehyde 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 relationship (QSAR) has been obtained to describe the cytotoxicity of 13 polyphenolic antioxidants belonging to three different groups (flavonoids, derivatives of gallic and caffeic acid): log cL50 (microM) = (2.7829+/-0.2339)+(1.2734+/-0.4715) Ep/2 (V)-(0.3438+/-0.0582) log P (r2 = 0.8129), where cL50 represents the concentration for 50% cell survival, Ep/2 represents the voltammetric midpoint potential, and P represents the octanol/water partition coefficient. Analogous QSARs were obtained using enthalpies of single-electron oxidation of these compounds, obtained by quantum-mechanical calculations. These findings clearly point to two important characteristics determining polyphenol cytotoxicity, namely their ease of oxidation and their lipophilicity.
Sergediene
E
E
Institute of Biochemistry, Mokslininku, Lithuania.
Jönsson
K
K
Szymusiak
H
H
Tyrakowska
B
B
Rietjens
I M
IM
Cenas
N
N
D000975:Antioxidants / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D005419:Flavonoids / Q000633:toxicity*; D018922:HL-60 Cells / Q000166:cytology; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010636:Phenols / Q000633:toxicity*; D011108:Polymers / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D011108:Polymers