O. G. Shevchenko

Separation of racemic ortho-isobornylphenol into enantiomers and evaluation of their antioxidant activity

Racemic ortho-isobornylphenol was separated into enantiomers through diastereomeric camphanates. The absolute configuration of chiral centers of the isolated products was determined by X-ray studies. Antioxidant activity and membrane-protective properties of the enantiomers were studied on the model of H2O2-induced hemolysis of erythrocytes.

Membrane-protective properties of isobornylphenols-a new class of antioxidants

The membrane protective and membrane active properties and the antioxidative activity of new semisynthetic antioxidants—isobornylphenols were studied. The presence of oxidant and cytotoxic properties of the compounds were evaluated considering the degree of hemolysis of erythrocytes, either spontaneous or induced by hydrogen peroxide. All the studied compounds were found to have significant antioxidative activity in certain conditions. But their capacity to protect membrane erythrocytes from oxidative stress substantially depended on the structure and concentration of the compound. The highest membrane protective activity was observed for 2,6-diisobornyl-4-methylphenol, which has isobornyl in both of its ortho-positions. Scanning electron microscopy of blood erythrocyte surface architectonics confirmed the ability of the studied compounds to interact with the cell membrane and to change its structure. A relationship between erythrocyte morphological transformation according to bilayer-couple hypothesis depending on isobornylphenols membrane behavior and the cytotoxic effect of certain compound high concentrations reflected in low membrane protective activity in the model cell system was shown. The data obtained allow us to conclude that the biological activity of isobornylphenols is due to both their antioxidative properties and their ability to interact with the cell membranes.

Synthesis and membrane-protective activity of novel derivatives of α-mangostin at the C-4 position.

A series of new C-4-derivatives of α-mangostin has been synthesized with the use of Mannich reaction and alkylation with 4-bromomethyl-2,6-dialkylphenols. It has been shown on a model of H2O2-induced erythrocyte hemolysis that the Mannich bases containing morpholinomethyl and piperidinomethyl fragments differ from parent α-mangostin by their high antioxidant and membrane-protective activity.

Membrane protective properties of carboxy derivatives based on 2,6-diisobornyl-4-methylphenol

Toxicity, antioxidant activity, and membrane protective properties were studied on mammalian red blood cells for carboxy derivatives and esters of 2,6-diisobornyl-4-methylphenol in comparison with both diastereomers (meso-form and racemate) of this terpenophenol. The studies showed that all the synthesized compounds posses an antioxidant activity, however, the cytotoxicity of derivatives with a free carboxy group might be an obstacle to the use of these compounds in pharmacology. The most promising compound is methyl 4-hydroxy-3,5-diisobornylbenzoate distinguished by a low toxicity and high antioxidant and membrane protective activity, which is comparable to that of 2,6-diisobornyl-4-methylphenol.

Synthesis and membranoprotective properties of new disulfides with monoterpene and carbohydrate fragments

A cooxidation of carbohydrate and terpene thiols gives mixtures of disulfides containing 51—90% of the unsymmetric product. Membranoprotective and antioxidant properties of obtained unsymmetric and symmetric disulfides were evaluated based on their ability to inhibit the H2O2-induced hemolysis of erythrocytes, as well as the accumulation of secondary products of the peroxy oxidation of lipids and the oxidation of hemoglobin.

Synthesis of novel terpenophenol-chlorin conjugates and evaluation of their membranotropic and membrane-protecting properties

A series of conjugates has been synthesized by the reaction of methylpheophorbide a with ortho-alkylaminomethyl derivatives of 2-isobornyl-4-methylphenol; the terpenophenol fragment in the conjugates is attached to the methylpheophorbide a macrocycle by an amide bond formed upon the amidation of the 13(2)-ester group. A scanning electron microscopy study of the surface structure of erythrocytes incubated with these compounds confirmed their ability to interact with the cell membrane. It was found, based on the ability of the conjugates to inhibit the H2O2-induced hemolysis of erythrocytes and slow down the accumulation of the secondary lipid peroxidation products, that they possess membrane-protecting and antioxidant properties.

Synthesis and membrane protective activity of 4-alkoxymethyl-2,6-diisobornylphenols

Bromination of 2,6-diisobornyl-4-methylphenol gave the corresponding 4-bromomethyl derivative, whose reaction with alcohols resulted in 4-alkoxymethyl-2,6-diisobornylphenols. Their toxicity, membrane protective and antioxidant activity were tested using red blood cells of laboratory mice. The synthesized compounds do not exhibit cytotoxicity at the concentrations of 10 and 100 μmol L–1 and are characterized by high membrane protective and antioxidant activity in the concentrations of 1 and 10 μmol L–1.

The synthesis and membrane protective properties of sulfanyl imines derived from neomenthane and isobornane thiols

Neomenthane and isobornane thiol-derived sulfanyl imines were prepared in yields of up to 85%. On the basis of the capacity of the sulfanyl imines obtained to inhibit the H2H2- and AAPH-induced erythrocyte hemolysis and impede the accumulation of secondary products of lipid peroxidation and hemoglobin oxidation, they were shown to display membrane protective and antioxidant properties.

Synthesis and membrane-protective activity of 4-aminomethyl derivatives of 2,6-diisobornylphenol

A series of 4-aminomethyl derivatives of 2,6-diisobornylphenol containing tertiary and secondary amino groups were synthesized. Their toxicity and the membrane-protective and antioxidant activity were assessed using red blood cells of laboratory mice as the test object. These compounds were shown to exhibit high membrane-protective and antioxidant activity, which substantially depends on the structure of the substituent and the concentration of the substance.

Membrane protective properties of diastereomers of methylpheophorbide a 13(2)-N-n-octyl-N-(2-hydroxy-3-isobornyl-5-methylbenzyl)amide

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. The evaluation of the membrane protective and antioxidant activity of the individual diastereomers on the model of H2O2-induced hemolysis of blood erythrocytes showed that the stereochemistry of the isobornyl substituent in the synthesized conjugates did not influence their biological activity.