Conformational analysis: a tool for the elucidation of the antioxidant properties of ferulic acid derivatives in membrane models.
With the aim to search and design more effective and safe antioxidant molecules to be used as functional ingredients in cosmetic formulations for UV protection, we evaluated the antioxidant/radical scavenging activities of ferulic acid and of some alkyl ferulates in both acellular and cellular systems. Ferulic acid esters, equipotent as antioxidant in homogeneous phase, showed when tested in membranous systems (rat liver microsomes, rat erythrocytes) marked differences in antioxidant potency. The n-C(12) derivative was the most potent, followed by n-C(8), n-C(16) and branched C(8), and then by ferulic acid. A conformational study carried out by NMR and modelling, indicates that the different antioxidant activity of ferulates in membrane models is due to the different spatial conformation and arrangement of the side chain of the molecule, which governs the access and binding to the phospholipid bilayer, the modality of orientation of the scavenging/quenching nucleus (phenol moiety), and hence the overall antioxidant potency of the derivative. These results emphasize the need of analytical studies (NMR and molecular modelling) addressed to the knowledge of the conformational parameters in combination with conventional antioxidant testings for understanding the antioxidant behaviour of a molecule in a biological membrane/system.
Anselmi
Cecilia
C
Dipartimento Farmaco Chimico Tecnologico, Università di Siena, Via Aldo Moro, 53100 Siena, Italy. anselic@unisi.it
Centini
Marisanna
M
Andreassi
Marco
M
Buonocore
Anna
A
La Rosa
Caterina
C
Facino
Roberto Maffei
RM
Sega
Alessandro
A
Tsuno
Fumi
F
D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D003373:Coumaric Acids / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000975:Antioxidants; D003373:Coumaric Acids; D004952:Esters; C004999:ferulic acid