title: Antioxidant-based lead discovery for cancer chemoprevention: the case of resveratrol.
abstract: Resveratrol is a well-known natural antioxidant and cancer chemopreventive agent that has attracted much interest in the past decade. Resveratrol-directed compounds were synthesized, and their antioxidant effects against reactive oxygen species (ROS)-induced DNA damage, their prooxidant effects on DNA damage in the presence cupric ions, and their cytotoxic and apoptosis-inducing effects on human promyelocytic leukemia (HL-60) cells were investigated in vitro. It was found that the compounds bearing o-diphenoxyl groups exhibited remarkably higher activities in inhibiting ROS-induced DNA damage, accelerating DNA damage in the presence cupric ions, and inducing apoptosis of HL-60 cells compared with the ones bearing no such groups. The detail mechanism of the structure-activity relationship was also studied by the oxidative product analysis of resveratrol and its analogues with galvinoxyl radical or cupric ions and UV-visible spectra change in the presence cupric ions. This study reveals a good and interesting correlation between antioxidant and prooxidant activity, as well as cytotoxicity and apoptosis-inducing activity against HL-60 cells, and provides an idea for designing antioxidant-based cancer chemoprevention agents.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Qian
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Cai
authors.forename: Gui-Juan
authors.initials: GJ
authors.lastname: Fan
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Zheng
authors.forename: Xiu-Zhuang
authors.initials: XZ
authors.lastname: Li
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Fang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D002413:Cations, Divalent; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000494:pharmacology; D004249:DNA Damage; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016877:Oxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002413:Cations, Divalent; D016877:Oxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D003300:Copper; D006861:Hydrogen Peroxide; D000077185:Resveratrol