Structure-activity relationship studies of resveratrol and its analogues by the reaction kinetics of low density lipoprotein peroxidation.
Resveratrol (3,5,4'-trans-trihydroxystibene) is a natural phytoalexin present in grapes and red wine, which possesses a variety of biological activities including antioxidative activity. To find more active antioxidants, with resveratrol as the lead compound, we synthesized resveratrol analogues, i.e., 3,4,3',4'-tetrahydroxy-trans-stilbene (3,4,3',4'-THS), 3,4,4'-trihydroxy-trans-stilbene (3,4,4'-THS), 2,4,4'-trihydroxy-trans-stilbene (2,4,4'-THS), 3,3'-dimethoxy-4,4'-dihydroxy-trans-stilbene (3,3'-DM-4,4'-DHS), 3,4-dihydroxy-trans-stilbene (3,4-DHS), 4,4'-dihydroxy-trans-stilbene (4,4'-DHS), 3,5-dihydroxy-trans-stilbene (3,5-DHS) and 2,4-dihydroxy-trans-stilbene (2,4-DHS). Antioxidative effects of resveratrol and its analogues against free-radical-induced peroxidation of human low density lipoprotein (LDL) were studied. The peroxidation was initiated either by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), or by cupric ion (Cu(2+)). The reaction kinetics were monitored either by the uptake of oxygen and the depletion of alpha-tocopherol (TOH) presented in the native LDL, or by the formation of thiobarbituric acid reactive substances (TBARS). Kinetic analysis of the antioxidation process demonstrates that these trans-stilbene derivatives are effective antioxidants against both AAPH- and Cu(2+)-induced LDL peroxidation with the activity sequence of 3,4,3',4'-THS approximately 3,3'-DM-4,4'-DHS>3,4-DHS approximately 3,4,4'-THS>2,4,4'-THS>resveratrol approximately 3,5-DHS>4,4'-DHS approximately 2,4-HS, and 3,4,3',4'-THS approximately 3,4-DHS approximately 3,4,4'-THS>3,3'-DM-4,4'-DHS>4,4'-DHS>resveratrol approximately 2,4-HS>2,4,4'-THS approximately 3,5-DHS, respectively. Molecules bearing ortho-dihydroxyl or 4-hydroxy-3-methoxyl groups possess significantly higher antioxidant activity than those bearing no such functionalities.
Cheng
Jin-Chun
JC
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
Fang
Jian-Guo
JG
Chen
Wei-Feng
WF
Zhou
Bo
B
Yang
Li
L
Liu
Zhong-Li
ZL
D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry*; D003300:Copper / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000737:chemistry*; D015394:Molecular Structure; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013997:Time Factors; D024502:alpha-Tocopherol / Q000737:chemistry
D000975:Antioxidants; D008077:Lipoproteins, LDL; D013267:Stilbenes; D003300:Copper; D024502:alpha-Tocopherol; D000077185:Resveratrol