Antioxidant-Based Lead Discovery for Cancer Chemoprevention: The Case of Resveratrol (Retracted Article. See vol 52, pg 6504, 2009)

State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu, China.
Journal of Medicinal Chemistry (Impact Factor: 5.48). 05/2009; 52(7):1963-74. DOI: 10.1021/jm8015415
Source: PubMed

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.