Formation and biological targets of botanical o-quinones

• Published in: Food and chemical toxicology 2018-10, Vol.120, p.700-707
• Main Authors: Bolton, Judy L., Dunlap, Tareisha L., Dietz, Birgit M.
• Format: Article
• Language: English
• Subjects: Activation, Metabolic; Alkylation; Bioactivation; Botanicals; Carcinogen; Chemoprevention; DNA - chemistry; Glutathione - chemistry; Hydroxylation; Oxidation-Reduction; P450; Plants - chemistry; Proteins - chemistry; Quinones; Quinones - chemical synthesis; Quinones - chemistry; Quinones - pharmacology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2018.07.050

The formation of o-quinones from direct 2-electron oxidation of catechols and/or two successive one electron oxidations could explain the cytotoxic/genotoxic and/or chemopreventive effects of several phenolic botanical extracts. For example, poison ivy contains urushiol, an oily mixture, which is oxidized to various o-quinones likely resulting in skin toxicity through oxidative stress and alkylation mechanisms resulting in immune responses. Green tea contains catechins which are directly oxidized to o-quinones by various oxidative enzymes. Alternatively, phenolic botanicals could be o-hydroxylated by P450 to form catechols in vivo which are oxidized to o-quinones. Examples include, resveratrol which is oxidized to piceatannol and further oxidized to the o-quinone. Finally, botanical o-quinones can be formed by O-dealkylation of O-alkoxy groups or methylenedioxy rings resulting in catechols which are further oxidized to o-quinones. Examples include safrole, eugenol, podophyllotoxin and etoposide, as well as methysticin. Once formed these o-quinones have a variety of biological targets in vivo resulting in various biological effects ranging from chemoprevention -> no effect -> toxicity. This U-shaped biological effect curve has been described for a number of reactive intermediates including o-quinones. The current review summarizes the latest data on the formation and biological targets of botanical o-quinones. [Display omitted] •o-Quinone formation could explain numerous biological effects of phenolic botanical compounds.•o-Quinones are alkylating agents and redox active compounds that can alkylate/oxidize key proteins, GSH, and/or DNA.•Three major mechanisms for o-quinone formation are presented.•Several botanicals form o-quinones through these mechanisms explaining the biological effects of the parent compounds.