The structure of 2-ethyl-3-hydroxy-6-methylpyridinium nitroxysuccinate (2) was studied. The cytotoxicity of this compound and its ability to have an effect on the level of intracellular nitrogen monoxide, as well as on the formation of reactive oxygen species and lipid peroxidation processes under conditions of induced oxidative stress, were evaluated. It was found that compound 2 has low in vitro cytotoxicity in normal and cancer cell models. It was shown that compound 2 can increase the level of intracellular nitrogen monoxide due to the presence of nitroxysuccinate in its structure. Compound 2 suppresses the lipid peroxidation in mouse brain homogenate in contrast to 2-ethyl-3-hydroxy-6-methylpyridinium succinate (1) . Besides, compound 2 more effectively reduces the level of intracellular reactive oxygen species under tert -butyl peroxide-induced oxidative stress and has a greater ability to bind superoxide compared to compound 1 . The results of this study show that compound 2 is promising for the development of drugs with antioxidant activity.

Water-soluble polymer compositions of the lipophilic complex of cis -bis[(nitroxyethyl)-isonicotinamide- N ]-tetrachloroplatinum( iv ) with antitumor activity were prepared. The complex was solubilized by amphiphilic copolymers of N -vinylpyrrolidone (VP) with (di)methacrylates synthesized by radical copolymerization in toluene in the absence of any inhibitors of polymer chain growth. Aqueous buffer solutions of the nanostructures were studied by dynamic light scattering, and the influence of the concentrations of the complex and copolymer and temperature on the nanoparticle size (hydrodynamic radius) was estimated. The nanostructures based on the VP copolymer with triethylene glycol dimethacrylate are shown to be thermosensitive and decompose when the temperature rises to physiologically significant values. According to the TEM data, the polymer particles are spherical and contain inclusions of the Pt IV complex ∼4 nm in size. The polymer compositions were studied using CV, TGA, and DSC methods. The results of IR spectroscopic analysis of the polymer compositions and quantum chemical modeling indicate the formation of the hydrogen bond between the NH groups of the complex and VP copolymer.

In the case of various pathologies, an imbalance between ROS generation and the endogenous AOS can be observed, which leads to excessive ROS accumulation, intensification of LPO processes, and oxidative stress. For the prevention of diseases associated with oxidative stress, drugs with antioxidant activity can be used. The cytotoxic, antioxidant, and NO-donor properties of the new hybrid compound B6NO (di(3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridinium) salt of 2-(nitrooxy)butanedioic acid) were studied. It was determined that B6NO chelates iron ions by 94%, which indicates B6NO's ability to block the Fenton reaction. The hybrid compound B6NO inhibits the process of initiated lipid peroxidation more effectively than pyridoxine. It was shown that B6NO exhibits antioxidant properties by decreasing ROS concentration in normal cells during the oxidative stress induction by tert-Butyl peroxide. At the same time, the B6NO antioxidant activity on tumor cells was significantly lower. B6NO significantly increases the intracellular nitrogen monoxide accumulation and showed low cytotoxicity for normal cells (IC50 > 4 mM). Thus, the results indicate a high potential of the B6NO as an antioxidant compound.

New hybrid macromolecular nanostructures of C60 fullerene based on an amphiphilic copolymer of N-vinylpyrrolidone with lauryl methacrylate and triethylene glycol dimethacrylate were prepared in isopropyl alcohol.

The effect of N-nitroxymethyl succinimide (1) , N-(2-nitroxyethyl) succinimide (2 ) and N-(3-nitroxypropyl) succinimide (3) on enzymatic activity of cyclic guanosine monophosphate (cGMP) phosphodiesterase was studied and crystal structure of compound (2) was determined. It was shown that all studied N-nitroxy succinimides inhibited cGMP phosphodiesterase in a concentration range of 0.1-0.001 mM. Compound (2) noncompetitively and reversibly inhibited hydrolytic function of enzyme with K i =1.7×10 —5 М. Inhibition constant for the reference compound N-(2-nitroethyl) nicotinamide (nicorandil) was 3×10 —5 М.

New cis-bis[N-(2-nitroxyethyl)isonicotinamide-N]platinum(iv) tetrachloride hybrid materials were obtained via its solubilization by nanoparticles of N-vinylpyrrolidone copolymer with dimethacrylates and characterized. The materials containing 2% of PtIV complex cause a cytotoxic effect on the tumor A-172 cells; IC50 values were ca. 106μm after incubation for 48h.

The nitrite-generating activity of 2-ethyl-3-hydroxy-6-methylpyridinium 2-nitroxysuccinate as a promising NO-donor has been investigated in reactions with various reducing agents. Reduction of the NO-donor with cysteine was analyzed using a kinetic modeling method. The calculated rate constants satisfactorily describe the experimental data, thereby confirming the proposed reaction mechanism.

We studied membranotropic properties of NO donor 2-nitroxysuccinate 3-hydroxy-6-methyl-2-ethylpyridine and its structural analog succinate 3-hydroxy-6-methyl-2-ethylpyridine (Mexidol). It was shown that the compounds under study are incorporated into modeled membranes and form long-living complexes with pyrene in the region of fatty acid tails of phospholipids. Luminol-amplified chemiluminescence analysis showed that both compounds exhibited antiradical activity and in a concentration of 0.1 mM reduced chemiluminescence intensity by more than 70%. 2-Nitroxysuccinate 3-hydroxy-6-methyl-2-ethylpyridine inhibited catalytic activity of monoamine oxidase A more efficiently than its structural analogue Mexidol.

The ability of the 2-nitroxysuccinate 3-hydroxy-6-methyl-2-ethylpyridine (I) compound to generate nitrite ions (NO2) and nitrogen monoxide (NO) in model systems with cysteine (Cys) and deoxyhemoglobin (Hb) has been studied. It has been established that there is a more efficient release NO2 and NO from compound I than from Nicorandil. The accumulation rate is 1.5 times higher in the system of Cys with I than with Nitroglycerin. It is shown that, unlike Nitroglycerin, compound I is not reduced by Hb.

A series of amino acid derivatives of oxalic acid were obtained. In combination therapy with conventional cytostatics used in lower doses, the new compounds substantially increase the efficacy of the drugs in the treatment of experimental P388 murine leukemia and some its drug-resistant strains.

Monoand disubstituted N-hydroxyamides of dicarboxylic acids were prepared by reaction of dicarboxylic acids or acid anhydrides with hydroxylamine. The use of these compounds in combinatorial cytostatic therapy of implanted tumors with cisplatin or cyclophosphamide totally inhibits metastasis formation in B16 melanoma and Lewis lung carcinoma, and resulted in 100% survival of leukemic animals.

Interaction of hydroxymethylnitrodiethylmalonate with ammonia produced, in contrast to published data, the ammonium salt of nitrodiethylmalonate; catalytic reduction of this compound with hydrogen followed by treatment with the chloranhydride of the 2-nitroxyethyl ester of succinamic acid yielded 2-nitroxyethylsuccinylaminodiethylmalonate. The final structures of the ammonium salt of nitrodiethylmalonate and 2-nitroxyethylsuccinylaminodiethylmalonate were identified by x-ray diffraction analysis.

The effect of mexidol (M) and nitroxymexidol (NM) on the activity of phosphodiesterase of cyclic guanosine monophosphate (PDEcGMP), regulation of lipid peroxidation (LPO), and antiradical and antihypoxic activity was investigated under normoxia and normobaric hypercapnic hypoxia conditions. Reversible and noncompetitive inhibition of the hydrolytic function of PDEcGMP by M and NM was revealed. The Ki value for M was 1 ×10–4 M; for NM, 1 ×10–5 M, i.e., NM was 10 times more active than M. It was shown that the lifetime of experimental animals in a closed space increased by 36% under the action of M as compared with that of the control group while it increased by 53% for NM. The ventricular contraction time increased by 137% for NM. The atrial contraction time increased from 31 min in the control to 52 and 57 min for M and NM, respectively.

Combinations of the known cytostatic cyclophosphamide (cyclophosphan) with hydroxamic acids (asparagylhydroxamic and salicylhydroxamic), nitric oxide donor (sodium nitrate), and an original hybrid non-steroidal anti-inflammatory compound, viz. , diclofenachydroxamic acid nitrate salt (DHA·HNO 3 ), were studied. The use of cyclophosphan in combination with these substances increases the efficiency of chemotherapy and elongates the life of animals with leukemia P-388. The dynamics of changes in the signal from cytochrome P-450 in the liver samples after the administration of DHA·HNO 3 to the animals was studied by ESR spectroscopy. The mechanism of the action of DHA·HNO 3 enhancing the chemotherapeutic effect of cyclophosphan was proposed.

A number of dicarboxylic N -(2-nitroxyalkyl)amides and N -(2-nitroxyalkyl)imides were synthesized and their antiischemic activity was studied. The ratio of the areas of necrotic and ischemic zones was used as a criterion for evaluation of antiischemic activity. The maximum values were close to antiischemic activity of Nicorandil, with acute toxicity of compounds synthesized being considerably lower.

A previously unknown palladium complex was synthesized by the reaction of 4-amino-2,2,6,6-tetramethylpiperidine with PdCl 2 . The X-ray diffraction study showed that the complex formed by 4-amino-2,2,6,6-tetramethylpiperidine with PdCl 2 is a chelate, in which the bidentate ligand adopts a boat conformation with the nitrogen atoms occupying cis positions at the palladium atom. The resulting cis -[4-amino-2,2,6,6-tetramethylpiperidine- N,N ′]dichloro-palladium( ii ) complex exhibits strong antimetastatic activity against experimental B16 melanoma at moderate toxicity.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Regioselective cyclocondensation of glycine hydroxamic and dl -alanine hydroxamic acids with 1-methylpiperidin-4-one gave 1-hydroxy-8-methyl-1,4,8-triazaspiro[4.5]decan-2-one ( 5 ) and (±)-1-hydroxy-3,8-dimethyl-1,4,8-triazaspiro[4.5]decan-2-one ( 6 ), respectively. The X-ray diffraction data showed that acid 6 formed racemic crystals with two independent molecules, whose structure was studied and compared with the analog obtained earlier. The in vivo tests on the leukemia P388 and L1210 models showed that the low-toxic spirocyclic hydroxamic acids 5 and 6 were the adjuvants of clinic cytostatics cisplatin and cyclophosphamide. Chemotherapy of the leukemias P388 and L1210 was more efficient with the combination of acid 6 with cisplatin and cyclophosphamide, respectively.