R. A. Kotel’nikova

Study of the neuroprotective action of hybrid structures based on fullerene C60

The neuroprotective action of hybrid structures based on fullerene C60 with attached proline amino acid has been studied. Hybrid structures contained natural antioxidant carnosine or addends with one or two nitrate groups. It has been shown that all studied compounds had antioxidant activity and decreased the concentration of malondialdehyde in homogenates of the rat brain. Compound I, which contained the antioxidant carnosine, has been found to be the most effective antioxidant. All compounds except IV and V inhibited the activity of monoamine oxidase B, while compounds I–IV increased the activity of monoamine oxidase A. All investigated compounds inhibited glutamate-induced Ca2+ uptake into synaptosomes of the rat brain cortex. Compound III, containing two nitrate groups, has been found to be the most effective inhibitor. This compound caused a significant increase of the currents of AMPA receptors (AMPA, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid).

Estimation of membrane activity of water-soluble polysubstituted fullerene derivatives by luminescence methods

Patterns of the interaction between water-soluble polysubstituted fullerene derivatives (PFDs) and the lipid bilayer of phosphatidylcholine liposomes were investigated by applying triplet and fluorescent probes. Objective quantitative criteria have been proposed for the evaluation of membranotropic action of chemical substances, notably, fullerene derivatives that quench fluorescent probes with different localizations within the membrane. Thus, the defined criteria are the rate constants for the quenching of the fluorescence of triplet probes and the equilibrium constants for PFD-probe complexes, which characterize their stability. The localization of PFDs in the membrane was determined by comparing rate constants for the quenching of eosin phosphorescence and equilibrium constants for PFD-chromophore complexes. In addition, the efficiency of the interaction of PFDs with various sites of the phospholipid membrane has been seen to depend on the charge of addends that are attached to the polysubstituted derivatives.

Design of a hybrid nanostructure based on fullerene C60 and biologically active substance for modeling physiological properties of compounds

The effects of cognitive-stimulating substance BD-2 of the γ-carboline family and a hybrid compound based on fullerene C60 and attached BD-2 on various aspects of the behavior of animals were studied. The synthesized hybrid fullerene compound (HFC) has no side psychostimulating effect characteristic of BD-2 but fully retains the properties of a cognitive-stimulating agent. The design of hybrid compounds based on fullerene C60 and pharmacologically active groups can be one of the ways for optimizing therapeutically promising compounds.

Effect of lipophilicity of C60 fullerene derivatives on their ability to inhibit peroxide oxidation of lipids in aqueous medium

The aqueous solutions of C60 fullerene derivatives were studied by means of dynamic light scattering, their effect on the peroxide oxidation of lipids (POL) in aqueous solutions was investigated via chemiluminescence method. It was shown that the colloidal solubility in water, which defines the antioxidant activity of C60 fullerene derivatives during POL, is controlled by the chemical structure of the addend added to C60 fullerene. For the studied derivatives, the direct dependence of the efficiency of POL inhibition on the lipophilicity was established.

Luminescent techniques in investigation of the biological properties of fullerene-based hybrid nanostructures

It has been shown that amino acid derivatives of C60 fullerene (ADFs) are effective quenchers of phosphorescence of the triplet probes eosin and erythrosine. The rate constants of erythrosine phosphorescence quenching by ADFs in aqueous solutions and model membranes have been determined. Using the triplet probe technique, the ability of ADFs to be transported across the lipid bilayer into the inner space of liposomes have been revealed. By monitoring a change in the fluorescence intensity of a luminescent hybrid structure based on C60-proline and eosin, the distribution of the hybrid structure in animal organs was established. The stability of hybrid structures subjected to various chemical and biological impacts was studied by recording the fluorescence of a Gd@C82-based hybrid structure.

Membranotropic properties of fullerene-containing amphiphilic (co)polymers of N-vinylpyrrolidone

The effect of fullerene-containing amphiphilic (co)polymers of N-vinylpyrrolidone (C60/PVP) differed in composition and topology of the polymer chains on the membrane structure of phosphatidylcholine liposomes was studied. Using the method of fluorescent probes it was found that the C60/PVP structures under study are localized in the phosphatidylcholine membrane in the region of glycerol fragments and fatty acid chains of phospholipids. The C60/PVP copolymers form complexes with 2,7-dibromoproflavin and pyrene probes. The effective equilibrium constants of the probe–C60/PVP complexes in aqueous solutions and in the liposome membrane were determined. It is most likely that the fullerene-containing (co)polymers of N-vinylpyrrolidone form complexes not only with fluorescent probes but also with phospholipids of the liposome membrane, which reduces the stability of the probe–C60/PVP complex.

Effect of fluorinated tetrahydrocarbazole derivatives on the enzymes of oxidative deamination of biogenic amines and on the process of lipid peroxidation

The effect of two fluorinated derivatives of tetrahydrocarbazoles on mitochondrial en-zymes catalyzing the oxidative deamination of biogenic amines such as monoamine oxidase A and B (MAO-A and MAO-B) has been investigated. A dose-dependent effect of the studied compounds on the enzymatic activity MAO-A was shown. It was revealed that both com-pounds are MAO-B inhibitors. Inhibition mechanisms were established and MAO-B inhibi-tion constants were calculated. The above derivatives exhibit strong antioxidant and antirad-ical activity.

Surface enhanced Raman scattering detection of water-soluble derivatives of fullerene C60 and their covalent conjugates with dyes in biological model systems

The potential of surface enhanced Raman spectroscopy (SERS) for the detection of water-soluble fullerene derivatives and their covalent conjugates with xanthene dyes was investigated in model biological liposome membranes and in the albumin protein structure. It was shown that in liposomes and in albumin, fullerene derivatives and their covalent conjugates with dyes show characteristic SERS spectra, which allows detection of water-soluble fullerene derivatives in phosphatidylcholine liposomes at the lipid/fullerene derivative ratio of 100 as well as fullerene–dye conjugates in liposomes and albumin.

Creation of a donor-acceptor pair for studying intraprotein electron transfer with the participation of amino-acid derivatives of fullerene C60

Efficient quenching of eosin phosphorescence by amino-acid derivatives of fullerene (AADFs) such as C60-alanine and C60-glycine in aqueous solutions indicates the possibility of transferring electrons from eosin to fullerene upon collisions or in the exciplex state. To investigate electron transfer in the protein structure, we studied the process of incorporation of C60-alanine and C60-glycine into the heme pocket of myoglobin by controlling Förster quenching. The dissociation constant for the protein-AADF complex was estimated.

812 - Inhibitory effect of radiosensltizer AK-2123 on experimental hepatic metastases and CA2+ active transport

A triazole group radiosensitizer AK-2123 is shown to inhibit considerably the growth of hepatic metastases induced by the intrasplenic injection of colon adenocarcinoma cells in syngenic mice. Even an extremely low dose of the drug exhibits the antimetastatic effect. It is shown that AK-2123 injected at therapeutic dose inhibits active transport of calcium ions by the (Ca2+-Mg2+)-dependent ATP-ase. The antimetastatic effect of AK-2123 is suggested to be related, at least partially, to the inhibition of the active calcium transport.