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

FEBS Letters

Sergedien≐, Egl≐⁴  Szymusiak, Henryk¹  Rietjens, Ivonne M.C.M.²  Č≐nas, Narimantas⁴  Tyrakowska, Bozena¹  Jönsson, Kerstin³ 

[1] Faculty of Commodity Science, Poznan University of Economics, Al. Niepodleglosci 10, Poznan 60967, Poland;Laboratory of Biochemistry and Division of Toxicology, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands;KFC Novum, Department of Hematology of Huddinge Hospital and Karolinska Institutet, S-141 86 Huddinge, Sweden;Institute of Biochemistry, Mokslinink 12, Vilnius 2600, Lithuania

关键词: Flavonoid;    Polyphenol;    Antioxidant;    Cytotoxicity;    Oxidative stress;    cL50;    concentration of agent for 50% cell survival;    P;    octanol/water partition coefficient;    E p/2;    voltammetric midpoint potential;    E 1;    single-electron oxidation potential;    ΔHf;    enthalpy of reaction;    DPPD;    N;    N′-diphenyl-p-phenylene diamine;   

DOI  :  10.1016/S0014-5793(99)01561-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (μM)=(2.7829±0.2339)+(1.2734±0.4715) E _p/2 (V)−(0.3438±0.0582) log P (r ²=0.8129), where cL₅₀ 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.

【 授权许可】

Unknown