Structure-antioxidant activity relationships in a series of NO-donor phenols.
Recently we reported a new class of NO-donor phenols that could be of interest in the treatment of many forms of cardiovascular disease (CD). Their potencies as inhibitors of ferrous salt/ascorbate-induced peroxidation of membrane lipids of rat hepatocytes were assessed as pIC(50) values through the TBARS assay. In this work we aimed to find quantitative relationships between the antioxidant activity of these compounds and appropriate molecular descriptors. In particular, we determined their log P(oct), their reactivity (log Z) in reaction with the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(.)), and the theoretical parameter DeltaH(abs), which describes the enthalpy of homolytic O--H bond cleavage. The QSAR equations found through the classical Hansch approach allowed us to draw interesting conclusions on the possible mechanisms of reaction with radicals in the various environments, while underlining the role of lipophilicity in antioxidant activity.
Tosco
Paolo
P
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, 10125 Torino, Italy.
Marini
Elisabetta
E
Rolando
Barbara
B
Lazzarato
Loretta
L
Cena
Clara
C
Bertinaria
Massimo
M
Fruttero
Roberta
R
Reist
Marianne
M
Carrupt
Pierre-Alain
PA
Gasco
Alberto
A
D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry*; D001713:Biphenyl Compounds; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005609:Free Radicals / Q000737:chemistry; D015394:Molecular Structure; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000737:chemistry*; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry*; D010851:Picrates / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism; D013816:Thermodynamics; D013997:Time Factors
D000975:Antioxidants; D001713:Biphenyl Compounds; D005609:Free Radicals; D020030:Nitric Oxide Donors; D010636:Phenols; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl