Free radical scavenging and antioxidant activities of substituted hexahydropyridoindoles. Quantitative structure-activity relationships.
New synthetic substituted hexahydropyridoindoles were studied for their radical scavenging ability in a system of an ethanolic solution of alpha,alpha'-diphenyl-beta-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 alpha,alpha'-diphenyl-beta-picrylhydrazyl, the sum of aromatic substitution constants (sigma(+)) 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.
Rackova
Lucia
L
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dubravska cesta 9, 84104 Bratislava, Slovakia. exfadada@savba.sk
Snirc
Vladimir
V
Majekova
Magdalena
M
Majek
Pavol
P
Stefek
Milan
M
D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D000975:Antioxidants; D016166:Free Radical Scavengers; D008081:Liposomes; D011725:Pyridines