ABSTRACT
We have studied the distribution of the new compound 4-methyl-2,6-diisobornylphenol in rats after a single oral administration in a dose of 20 mg/kg. The pharmacokinetic parameters have been estimated by the noncompartmental method. It is established that the drug is nonuniformly distributed in the body and has a high affinity for liver and heart. A low penetration of 4-methyl-2,6-diisobornilphenol has been found in brain tissue. The accumulation of 4-methyl-2,6-diisobornilphenol in adipose tissues has not been found. It been showed that the drug is slowly eliminated from the body, especially from the heart tissues for which the mean retention time is MRT = 45 h.
Subject(s)
Camphanes/pharmacokinetics , Cresols/pharmacokinetics , Fibrinolytic Agents/pharmacokinetics , Adipose Tissue/metabolism , Administration, Oral , Animals , Brain/metabolism , Camphanes/blood , Cresols/blood , Female , Fibrinolytic Agents/blood , Kidney/metabolism , Liver/metabolism , Male , Muscles/metabolism , Myocardium/metabolism , Rats , Rats, Wistar , Tissue DistributionABSTRACT
The linearity of pharmacokinetics of 4-methyl-2,6-diisobornylphenol after single intragastric administration in doses within 10 - 200 mg/kg has been studied in rats. It has been established that pharmacokinetics of 4-methyl-2,6-diisobornilphenol in the indicated dose range is not linear due to a limited absorption of the drug from the intestine.
Subject(s)
Antioxidants/pharmacokinetics , Camphanes/pharmacokinetics , Cresols/pharmacokinetics , Intestinal Mucosa/metabolism , Animals , Antioxidants/administration & dosage , Antioxidants/metabolism , Area Under Curve , Camphanes/administration & dosage , Camphanes/blood , Cresols/administration & dosage , Cresols/blood , Drug Administration Schedule , Intestinal Absorption/physiology , Male , Rats , Rats, Wistar , StomachABSTRACT
Two diastereomers of methylpheophorbide a 13(2)-N-n-octyl-N-(2-hydroxy-3-isobornyl-5-methylbenzyl)amide were obtained from (+)- and (-)-enantiomers of 2-isobornyl-4-methylphenol. Evaluation of membrane protective and antioxidant activity of individual diastereomers on the model of H2O2-induced hemolysis of blood erythrocytes showed that the stereochemistry of isobornyl substituent in the synthesized conjugates has no effect on their biological activity.
Subject(s)
Camphanes/chemistry , Chlorophyll/analogs & derivatives , Membranes/drug effects , Protective Agents/chemistry , Animals , Chlorophyll/chemical synthesis , Chlorophyll/chemistry , Chlorophyll/pharmacology , Chromatography, High Pressure Liquid , Cresols/chemistry , Erythrocytes/drug effects , Hydrogen Peroxide/chemistry , Mice , Molecular Structure , Protective Agents/chemical synthesis , Protective Agents/pharmacology , StereoisomerismABSTRACT
A series of terpenophenol-chlorin conjugates where terpenophenolic fragment has amide bond with macrocycle of methylpheophorbide a, formed by amidation of 13(2)-ester group were obtained by interaction of methylpheophorbide a and ortho-aminomethyl derivatives of 2-isobornyl-4-methylphenol. The substances investigated ability to interact with the cell membrane was shown in blood erythrocytes surface structure with scanning electron microscope. The conjugates studied were established to have antioxidant and membrane protective properties resulted from inhibiting H2O2-induced erythrocytes hemolysis and decrease of lipid peroxidation secondary product accumulation.
Subject(s)
Erythrocyte Membrane/chemistry , Hemolysis/drug effects , Hydrocarbons, Chlorinated , Lipid Peroxidation/drug effects , Phenols , Terpenes , Animals , Chlorophyll/analogs & derivatives , Chlorophyll/chemistry , Hydrocarbons, Chlorinated/chemical synthesis , Hydrocarbons, Chlorinated/chemistry , Hydrocarbons, Chlorinated/pharmacology , Mice , Phenols/chemical synthesis , Phenols/chemistry , Phenols/pharmacology , Terpenes/chemical synthesis , Terpenes/chemistry , Terpenes/pharmacologyABSTRACT
Interrelations between the structure of the semi-synthetic phenolic antioxidants -- isobornylphenols and their surface active properties were studied in the chemical (the lecithin aggregation in hexane) and biological (the incubation with the blood erythrocytes) model systems. It has been shown that all studied compounds are able to affect the lecithin aggregation in hexane: the share of the main fraction of the L micelles decreases with increasing the share of particles of greater size. The effect substantially depends on hindered OH group and the presence of the intramolecular hydrogen bond in molecule. The cytotoxic properties of isobornylphenols (the concentration is 100 M) are predominantly due to the molecule structure. The interrelation between the aggregate size of the main fraction of L in the presence of the studied compounds and the discocyte share during mice blood erythrocyte incubation in their presence for 4 h is revealed. Thus, this provides the possibility to assume that the ability of the different biological active substances to affect the lecithin aggregation in non-polar solvent could be used as a model system for the initial assessment of their surface active properties.
Subject(s)
Antioxidants/chemistry , Phenols/chemistry , Surface Properties , Animals , Erythrocytes , Hexanes/chemistry , Hydrogen Bonding , Lecithins/chemistry , Mice , Micelles , Molecular Structure , Solvents/chemistryABSTRACT
Water-soluble sulfate polysalts of carboxymethyl cellulose and tertiary aminomethyl derivatives of 2-isobornyl-4-methylphenol was obtained. For the synthesized conjugates investigated in vivo anti-inflammatory activity in the test of acute formalin inflammation and analgesic activity in tests the "hot plate" and "vinegar cramps".
Subject(s)
Carboxymethylcellulose Sodium , Inflammation , Pain Measurement/drug effects , Pain , Animals , Carboxymethylcellulose Sodium/analogs & derivatives , Carboxymethylcellulose Sodium/chemical synthesis , Carboxymethylcellulose Sodium/chemistry , Carboxymethylcellulose Sodium/pharmacology , Formaldehyde/toxicity , Inflammation/chemically induced , Inflammation/drug therapy , Mice , Pain/drug therapy , Pain/pathology , Solubility , Sulfates/chemical synthesis , Sulfates/chemistry , Sulfates/pharmacology , Water/chemistryABSTRACT
The pharmacokinetics of 4-methyl-2,6-diisobornylphenol (MDIBP) in rat blood plasma has been studied after intravenous injection. The drug concentration in the plasma was determined using a reverse-phase HPLC procedure. It is shown that MDIBP rapidly penetrates into intensively perfused organs, but is slowly eliminated from the organism (MRT value amounting to 9 h).
Subject(s)
Antioxidants/pharmacokinetics , Camphanes/pharmacokinetics , Cresols/pharmacokinetics , Models, Biological , Animals , Antioxidants/administration & dosage , Antioxidants/chemistry , Camphanes/administration & dosage , Camphanes/blood , Camphanes/chemistry , Cresols/administration & dosage , Cresols/blood , Cresols/chemistry , Injections, Intravenous , Male , Organ Specificity , Rats , Rats, Wistar , Tissue DistributionABSTRACT
Neuroprotective activity of the new sterically hindered phenolic antioxidant 4-methyl-2,6-diisobornylphenol (dibornol) in rats with total transient cerebral ischemia was investigated. Dibornol decreased mortality of rats and the number of animals with severe neurological deficit; moreover, it accelerated restoration of neurological status in the survived rats. Neuroprotective activity of dibornol is based on its ability to diminish lipid peroxidation in ischemic brain, suppress cerebral tissue hypoxia and protect functional activity of endothelium. Improved oxygen delivery was a consequence of reduced hyperviscosity syndrome (enhanced deformability of erythrocytes and their decreased aggregation).
