Design and synthesis of 2,6-diprenyl-4-iodophenol TX-1952 with a novel and potent anti-peroxidative activity.
The structure-based elucidation of 2,4,6-tri-substituted phenols for their antioxidative and anti-peroxidative effects has been investigated using TX-1952 (2,6-diprenyl-4-iodophenol), TX-1961, TX-1980, BTBP and BHT. In the inhibition of mitochondrial lipid peroxidation, the inhibitory activity of 2,6-di-tert-butyl-4-bromophenol (BTBP) (IC(50)=0.17 microM) was twice as high as that of 2,6-di-tert-butyl-4-methylphenol (BHT) (IC(50)=0.31 microM). This result shows that the 4-halogen group increases inhibitory activity for mitochondrial lipid peroxidation. Besides, TX-1952 (IC(50)=0.60 microM) was the highest inhibitor among 2,6-diprenyl-4-halophenols, followed by TX-1961 (IC(50)=0.93 microM) and TX-1980 (IC(50)=1.2 microM). In 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging experiments, the activity of TX-1952 (IC(0.200)=53.1 microM) was lower than that of BHT (IC(0.200)=33.7 microM) and BTBP (IC(0.200)=16.0 microM), but TX-1952 and BHT showed the same HOMO energy (-8.991 eV). These results suggest that the two prenyl groups at ortho position hinder the phenolic hydrogen abstraction by DPPH radical. These findings demonstrated that TX-1952 was a novel and potent inhibitor for lipid peroxidation.
Uto
Yoshihiro
Y
Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, Minamijosanjima-cho 2-1, Tokushima 770-8506, Japan.
Hirata
Akihiko
A
Ishibashi
Masaki
M
Nagasawa
Hideko
H
Hori
Hitoshi
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001713:Biphenyl Compounds; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007462:Iodobenzenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010851:Picrates / Q000378:metabolism; D051381:Rats
C472252:2,6-diprenyl-4-iodophenol; D000975:Antioxidants; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D007462:Iodobenzenes; D010636:Phenols; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl