Effect of methyl substitution on the antioxidative property and genotoxicity of resveratrol.
Resveratrol ( trans-3,4',5-trihydroxystilbene) is a natural phytoalexin with various biological activities including inhibition of lipid peroxidation and free radical scavenging properties. In addition to its beneficial effects, resveratrol also has significant genotoxicity that leads to a high frequency of chromosome aberration together with micronucleus and sister chromatid exchanges. To enhance the radical scavenging activities and to reduce the genotoxicity of resveratrol, we designed 4'-methyl resveratrol analogues where a methyl group was introduced at the ortho position relative to the 4'-hydroxy group, which is responsible for both antioxidative activities and genotoxicity of resveratrol. These synthesized methyl analogues of resveratrol showed increased antioxidative activities against galvinoxyl radical as an oxyl radical species. Furthermore, the methyl analogues also surprisingly showed reduced in vitro genotoxicities, suggesting that methyl substitution may improve resveratrol efficacy.
Fukuhara
Kiyoshi
K
Division of Organic Chemistry, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan. fukuhara@nihs.go.jp
Nakanishi
Ikuo
I
Matsuoka
Atsuko
A
Matsumura
Tomohiro
T
Honda
Sachiko
S
Hayashi
Mikiko
M
Ozawa
Toshihiko
T
Miyata
Naoki
N
Saito
Shinichi
S
Ikota
Nobuo
N
Okuda
Haruhiro
H
D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002869:Chromosome Aberrations / Q000139:chemically induced; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D008745:Methylation; D009153:Mutagens / Q000737:chemistry* / Q000633:toxicity; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000975:Antioxidants; D009153:Mutagens; D013267:Stilbenes; D000077185:Resveratrol