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Prooxidant toxicity of polyphenolic antioxidants to HL‐60 cells: description of quantitative structure‐activity relationships
Author(s) -
Sergedien≐ Egl≐,
Jönsson Kerstin,
Szymusiak Henryk,
Tyrakowska Bozena,
Rietjens Ivonne M.C.M.,
Č≐nas Narimantas
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01561-6
Subject(s) - chemistry , lipophilicity , polyphenol , cytotoxicity , quantitative structure–activity relationship , caffeic acid , gallic acid , stereochemistry , antioxidant , partition coefficient , medicinal chemistry , organic chemistry , biochemistry , in vitro
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 cL 50 (μM)=(2.7829±0.2339)+(1.2734±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 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.