Structural Modification Of Phenolic Antioxidants And Their Mechanisms Of Prooxidant Effects

Resveratrol (3,5,4'-trans-trihydroxystilbene) is a natural phytoalexin present in grapes and red wine, which possesses a variety of biological activities including antioxidative activity. On the other hand, it was reported that an antioxidant might become a prooxidant to accelerate lipid peroxidation and/or induce DNA damage under special conditions. The prooxidant effect of resveratrol (3,5,4'-trihydroxy-trans-stibene) an -d its synthetic analogues (ArOH), that is, 3,4,4'-trihydroxy-trans-stibene(3,4,4'-THS), 3,4,5-trihydroxy-trans-stibene (3,4,5-THS), 3,4-dihydroxy-trans-stibene (3,4-DHS), 4,4'-dihydroxy-trans-stibene(4,4'-DHS),3,5,4'-trimethoxy-trans-stibene(3,5,4'-TMS), 2,4-dihydroxy-trans-stilbene (2,4-DHS) and 3,5-dihydroxy-trans-stilbene (3,5-DHS) on supercoiled pBR322 plasmid DNA strand breakage and calf thymus DNA damage in the presence of Cu (II) ions has been studied. It was found that the compounds bearing ortho-dihydroxyl groups (3,4-DHS, 3,4,4'-THS, and 3,4,5-THS) or bearing 4-hydroxyl groups (2,4-DHS, 4,4'-DHS, and resveratrol) exhibit remarkably higher activity in the DNA damage than the ones bearing no such functionalities. Kinetic analysis by UVvisible spectra demonstrates that the formation of ArOH-Cu (II) complexes, the stabilization of oxidative intermediate derived from ArOH and Cu (II)/Cu (I) redox cycles, might be responsible for the DNA damage. This study also reveals a good correlation between antioxidant and prooxidant activity, as well as cytotoxicity against human leukemia (HL-60 and Jurkat) cell lines. The mechanisms and implications of these observations are discussed.Hydroxycinnamic acid derivatives, i.e., caffeic acid (CaA), 3-hydroxycinnamic acid (3-HCA), ferulic acid (FA), chlorogenic acid (ChA), sinapic acid (SA), and 4-hydroxycinnamic acid (4-HCA), are widely distributed in plants and are known as antioxidant of various food products. Their prooxidant effect was also studied in supercoiled pBR322 plasmid DNA strand breakage and calf thymus DNA damage in the presence of Cu(II)ions.In addition, the anticancer drugs of 1,1,2-triphenylalkenes have been synthesized by McMurry coupling reaction based on the parent tamoxifen. Their antiproliferati -ve effect on MCF-7 human breast cancer cells, HO-8910 human ovarian carcinoma cells, and HL-60 promyelocytic leukemia cells were studied by use of the MTT colorimetric or sulphorhodamine B (SRB) assay. Structure-activity relationship (SAR) analysis demonstrates that the methoxyl group on the 2-phenyl ring contributes critically to the activity.