Antioxidant Activity of Ferulic Acid Alkyl Esters in a Heterophasic System: A Mechanistic Insight

The antioxidant activity of some esters of ferulic acid with the linear fatty alcohols C7, C8 (branched
and linear), C9, C11, C12, C13, C15, C16, and C18 has been studied in homogeneous and heterogeneous
phases. Whereas in homogeneous phase all of the alkyl ferulates possessed similar radical-scavenging
abilities, in rat liver microsomes they showed striking differences, the more effective being C12 (7)
(IC50 = 11.03 μM), linear C8 (3) (IC50 = 12.40 μM), C13 (8) (IC50 = 18.60 μM), and C9 (5) (IC50 =
19.74 μM), followed by C7 (2), C15 (9), C11 (6), branched C8 (4), C16 (10), and C18 (11) (ferulic acid
was the less active, IC50 = 243.84 μM). All of the molecules showed similar partition coefficients in
an octanol-buffer system. Three-dimensional studies (NMR in solution, modeling in vacuo) indicate
that this behavior might be due to a different anchorage of the molecules with the ester side chain to
the microsomal phospholipid bilayer and to a consequent different orientation/positioning of the
scavenging phenoxy group outside the membrane surface against the flux of oxy radicals.
Keywords: Alkyl ferulates; antioxidant/radical scavenging activity; acellular and cellular models;
conformational analysis; intervention in biological membranes