Enhancement of antioxidant activity of p-alkylaminophenols by alkyl chain elongation

The initial finding that the p-methylaminophenol ( 6) exhibited antioxidant activity led us to investigate whether the length of alkyl chains linked to the aminophenol residue might affect antioxidative activity. Therefore, we synthesized p-butylaminophenol ( 5), p-hexylaminophenol ( 4), p-octylaminophenol ( 3), and p-methoxybenzylaminophenol ( 7). All p-alkylaminophenols quenched α,α-diphenyl-β-picrylhydrazyl (DPPH) radicals, with 7 being the most potent DPPH radical scavenger. Lipid peroxidation by rat liver microsomes was reduced by p-alkylaminophenols in dose- and aminophenol alkyl chain length-dependent fashion ( 3> 4> 5> 6), with 3 being the most potent lipid peroxidation inhibitor, at approximately 350-fold higher potency than 6. These results indicate that elongation of alkyl chains in p-alkylaminophenols may increase antioxidative activity, and that p-alkylaminophenols may potentially be useful in the development of antioxidants. 3 was the most potent lipid peroxidation inhibitor, at approximately 350-fold higher potency than 6.