Free Radical Scavenging and Antioxidant Activities of Substituted Hexahydropyridoindoles. Quantitative Structure−Activity Relationships

• Published in: Journal of medicinal chemistry 2006-04, Vol.49 (8), p.2543-2548
• Main Authors: Rackova, Lucia, Snirc, Vladimir, Majekova, Magdalena, Majek, Pavol, Stefek, Milan
• Format: Article
• Language: English
• Subjects: Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Biological and medical sciences; Computer Simulation; Drug Evaluation, Preclinical; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; General and cellular metabolism. Vitamins; Lipid Peroxidation - drug effects; Liposomes - metabolism; Medical sciences; Pharmacology. Drug treatments; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Quantitative Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm060041r

New synthetic substituted hexahydropyridoindoles were studied for their radical scavenging ability in a system of an ethanolic solution of α,α‘-diphenyl-β-picrylhydrazyl and for their lipid peroxidation inhibitory properties in a suspension of unilamellar dioleoylphosphatidylcholine liposomes. The activities in both in vitro systems were correlated with several structural parameters. In the homogeneous system of α,α‘-diphenyl-β-picrylhydrazyl, the sum of aromatic substitution constants (∑σ+) and the hydration energy were shown to be effective predictors of the radical scavenging activity of the hexahydropyridoindole derivatives. Moreover, in the heterogeneous system comprising a model liposomal membrane, the overall antioxidant activity of the compounds was affected by their lipid-phase availability governed by the lipophilicity and basicity of the molecules.