Comparative study on determination of antioxidant and membrane activities of propofol and its related compounds

• Published in: European journal of pharmaceutical sciences 2010-01, Vol.39 (1), p.97-102
• Main Authors: Tsuchiya, Hironori, Ueno, Takahiro, Tanaka, Toshiyuki, Matsuura, Nobuyasu, Mizogami, Maki
• Format: Article
• Language: English
• Subjects: alpha-Tocopherol - pharmacology; Anesthetics, Intravenous - chemistry; Anesthetics, Intravenous - pharmacology; Antioxidant; Antioxidants - chemistry; Antioxidants - pharmacology; Biological and medical sciences; Chromans - pharmacology; Fluidity modification; General pharmacology; In Vitro Techniques; Lipid peroxidation; Lipid Peroxidation - drug effects; Liposomes - metabolism; Medical sciences; Membrane Fluidity - drug effects; Membrane interactivity; Molecular Structure; Oxidative Stress - drug effects; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Propofol; Propofol - analogs & derivatives; Propofol - chemistry; Propofol - pharmacology; Structure-Activity Relationship; Superoxide Dismutase - antagonists & inhibitors; Superoxide Dismutase - metabolism
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2009.11.001

Certain anesthetics have been suggested to protect against the pathological states associated with oxidative stress. We compared the antioxidant and membrane activities of propofol (2,6-diisopropylphenol) and its related compounds to address the structure–activity relationship especially in a lipid membrane phase. They were studied for the effects on 1,1-diphenyl-2-picrylhydrazyl radicals, nitro blue tetrazolium reduction by superoxide anions and membrane lipid peroxidation by peroxynitrite, and also for the induced changes in membrane fluidity of liposomes. 2-Isopropylphenols scavenged free radicals with the potency being propofol > 2,5-diisopropylphenol > 2-isopropylphenol > 2,4-diisopropylphenol, but not 3- and 4-isopropylphenols and 1,3- and 1,4-diisopropylbenzenes. The tested compounds showed no significant superoxide dismutase-like effects. Propofol inhibited membrane lipid peroxidation more intensively than 2,5-diisopropylphenol, 2,4-diisopropylphenol and 2-isopropylphenol. Despite structurally resembling antioxidant α-tocopherol, 2,6-dimethylphenol was less potent than propofol. Propofol produced 50% inhibition of the lipid peroxidation in unsaturated phosphatidylcholine liposomal membranes and cell-mimetic membranes at 4.0 and 10.1 μM, respectively. Propofol and 2-alkylphenolic compounds interacted with membranes to increase their fluidity with the potency correlating with lipid peroxidation inhibiting activity. The 2-isopropylphenol structure is a requisite for both lipid peroxidation inhibition and membrane fluidity modification. The structure-specific membrane interactivity appears to be one of possible antioxidant mechanisms for propofol.