Antioxidative and 5-lipoxygenase inhibiting activities of novel bis(4-hydroxy-2,3,5-trimethylphenoxy)alkyl derivatives.
Novel bis(4-hydroxy-2,3,5-trimethylphenoxy)alkyl derivatives were synthesized and evaluations were made of their inhibiting action on Fe3+-ADP induced lipid peroxidation in rat liver microsome and reducing action on alpha,alpha-diphenyl-beta-picrilhydrazyl (DPPH), a stable radical, in addition to their inhibiting action on 5-lipoxygenase (5-LO), an enzyme that synthesizes leukotrienes. We performed a structure-activity correlation study on these derivatives. A strong Fe3+-ADP induced lipid peroxidation preventing activity was observed for the derivatives with an odd number of methylene groups including 1,3-bis(4-hydroxy-2,3,5-trimethylphenoxy)propane (3b) and 3a. No change in the DPPH reducing activity was found with change in the number of methylene groups. 5-LO inhibiting activity among the derivatives was the highest for 1,6-bis(4-hydroxy-2,3,5-trimethylphenoxy)hexane (3e). MM2 calculations were performed to find a stable steric structure for the derivatives, and 1,5-bis(4-hydroxy-2,3,5-trimethylphenoxy)pentane (3d) showed a strong activity in both antioxidative action and 5-LO inhibiting action.
Hirano
T
T
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
Kawasaki
N
N
Miyataka
H
H
Nishiki
M
M
Satoh
T
T
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D013057:Spectrum Analysis
D000975:Antioxidants; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors