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 α, α-diphenyl-β-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.