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 M), linear C8 (3) (IC50 = 12.40 microM), C13 (8) (IC50 = 18.60 microM), and C9 (5) (IC50 = 19.74 microM), 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 microM). 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.
Dipartimento Farmaco Chimico Tecnologico, Università di Siena, Via Aldo Moro, 53100 Siena, Italy. anselmic@unisi.it
Cecilia
C
Anselmi
Marisanna
M
Centini
Paola
P
Granata
Alessandro
A
Sega
Anna
A
Buonocore
Andrea
A
Bernini
Roberto Maffei
RM
Facino
D000478:Alkylation; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology*; D004952:Esters / Q000737:chemistry / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry; D010545:Peroxides / Q000737:chemistry; D010851:Picrates / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D001713:Biphenyl Compounds; D003373:Coumaric Acids; D004952:Esters; D005233:Fatty Alcohols; D010545:Peroxides; D010851:Picrates; C049375:perhydroxyl radical; C004999:ferulic acid; C004931:1,1-diphenyl-2-picrylhydrazyl