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The synthesis of new functionally substituted 1H-indene-1,3(2H)-diones, indenobenzofurans, and 2,5-benzodiazocines is described. The condensations of ninhydrin in concentrated sulfuric acid with 2-(mor­pholin-4-yl)ethyl and 2-(pyridin-2-yl)ethyl phenylcarbamates at 20°C and with 2,6-di-tert-butylphenol while gradually raising the temperature from 0 to 20°C gave the corresponding 2,2-disubstituted 1H-indene-1,3(2H)-diones in 62–89% yields. 6-(1-Adamantyl)-4b,9b-dihydroxy-8-methyl-4b,9b-dihydro-10H-indeno[1,2-b]benzo­furan-10-one and 6,3-di(tert-butyl)-4b,9b-dihydroxy-4b,9b-dihydro-10H-indeno[1,2-b][1]benzofuran-10-one were obtained with high yields (96–98%) by heating ninhydrin with 2-(1-adamantyl)-4-methylphenol and 2,4-di(tert-butyl)phenol, respectively, in glacial acetic acid at 60°C. Benzofurans containing an adamantyl, tert-butyl, or carbamate fragment reacted with 99% ethylenediamine at 20°C to afford 80–85% of new 2,5-benzo­diazocine derivatives.

The antioxidant and cryoprotective efficiencies of a 3,5-di-tert-butyl-4-hydroxyphenyl)methylenediphosphonic acid (MDPA) differ significantly for sperm cells of various species of sturgeon fish (Russian sturgeon, beluga and Stellate sturgeon). The ability of phosphorus-containing phenol MDPA to decrease the level of lipid peroxidation of sperm, beneficial effect on the activity indicators of the sperm of native sturgeon and of the defrosted one after deep freezing as well as on the fertility of sperm cells was shown.

5-Acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)-dione reacted with cyclohexyl and benzyl (4-aminophenyl)carbamates in boiling ethanol in the presence of a catalytic amount of glacial acetic acid to give the corresponding Schiff bases, cyclohexyl and benzyl (4-{[(E)-1-(4-hydroxy-2,6-dioxo-3,6-dihydro-2H-1,3-thiazin-5-yl)ethylidene]amino}phenyl)carbamates. Heating of the latter in dimethylformamide for 2 h was accompanied by evolution of COS with the formation of cyclohexyl and benzyl {4-[6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl]phenyl}carbamates. The condensation of the title compound with benzene-1,2-diamine in propan-2-ol, followed by addition of 5-arylfuran-2-carbaldehyde and trifluoroacetic acid afforded 5-(2-{5-[4-bromo(nitro)phenyl]furan-2-yl}-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-4-hydroxy-2H-1,3-thiazine-2,6(3H)-diones. 5-((E)-3-{5-[4-Bromo(nitro)phenyl]furan-2-yl}prop-2-enoyl)-4-hydroxy-2H-1,3-thiazine-2,6(3H)-diones were synthesized by condensation of 5-acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)-dione with 5-[4-bromo(nitro)phenyl]furan-2-carbaldehydes in chloroform in the presence of catalytic amounts of pyridine and piperidine.

The paper gives an assessment of biochemical composition of various types of returnable baking waste, pregrouped into five groups depending on recipe and bakery products production method, in comparison with traditional types of starch-containing raw materials — wheat and rye. It has been established that returnable baking waste has significant advantages over grain raw materials in terms of starch content and structural and mechanical properties, which will eliminate grinding cost. An analysis of carbohydrate complex of returnable baking waste showed that waste groups that include rye flour contain more glucose than groups derived from wheat flour, which can positively affect the fermentation process. The study of protein complex revealed that mass fraction of soluble protein was determined by type of raw material used to produce products. It is shown that the best raw materials for distillates production, from standpoint of protein complex evaluating, are samples of returnable baking waste products obtained from rye-wheat bread. The mineral composition (K+, Na+, Ca++, Mg++) of ash of various waste types was studied and it was found that products from wheat flour contain less potassium, calcium and magnesium than from rye-wheat, and no significant differences were found in sodium content. Identified distinctive features in biochemical composition of certain groups of returnable baking waste products are recommended to be taken into account when developing optimal technological regimes for their processing in distillates production.

Alcohol products are very popular in the consumer market, although it is not a highly needed and essential product. Cognac is one of the exquisite aristocratic and sophisticated beverage, its production consist of complex and lengthy technological process, on which an unique, full bouquet and aroma directly depend. This determines the importance of such aspects as obtaining a high quality and environmentally safe products that have some positive effect on the human body. Moreover, for cognac, the most important is the quality of the original wine materials and new production technologies, which form the organoleptic properties of the drink. The study of branded V.S. cognacs on the territory of the Russian Federation by organoleptic and instrumental methods of analysis showed that not all of them can be identified as French brandies.

The reaction of methyl N-{4-[2-(2-oxo-2,3-dihydro-1H-indol-3-ylidene)acetyl]phenyl}carbamate with tosylmethyl isocyanide in tetrahydrofuran in the presence of potassium tert-butoxide led to the formation of methyl N-{4-[(4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinolin-1-yl)carbonyl]phenyl}carbamate. Three-component condensation of methyl N-{4-[(E)-3-R-prop-2-enoyl]phenyl}carbamates and methyl N-{4-[2-(2-oxo-2,3-dihydro-1H-indol-3-ylidene)acetyl]phenyl}carbamate with sarcosine and paraformaldehyde in boiling toluene with simultaneous removal of water by azeotropic distillation afforded methyl N-(4-{4-[4-R-1-methyl-pyrrolidin-3-yl]carbonyl}phenyl)carbamates and methyl N-[4-(1′-methyl-2-oxo-1,2-dihydrospiro[indole-3,3′-pyrrolidin]-4′-ylcarbonyl)phenyl]carbamate, respectively.

The redox properties and antiradical activity of terpenophenols (2,6-diisobornyl-4-methylphenol and 3-isocamphyl-2-naphthol) in comparison with BHT (butylhydroxytoluene, 2,6-di-tert-butyl-4-methylphenol) have been studied. The terpenophenols have been shown to react more readily in electron transfer processes as compared with BHT, and they have been found to react with electrochemically generated superoxide radical anion ( $${\text{O}}_{2}^{{\centerdot - }}$$ ). The effect of the compounds on the rate of $${\text{O}}_{2}^{{\centerdot - }}$$ generation upon adrenaline oxidation in an alkaline medium and the ability of biopreparations based on Russian sturgeon liver and gonad homogenates to deactivate $${\text{O}}_{2}^{{\centerdot - }}$$ have been studied. Adrenaline oxidation inhibition and the increase in superoxide dismutation activity of the biopreparations in the presence of terpenophenols has been shown, and this fact can indicate the ability of these compounds to decrease the probability of oxidative stress enlargement. A correlation has been established between the redox properties and antioxidant activity of terpenophenols in the model system of adrenaline oxidation in the presence of the biopreparations.

1-(3,5-Di-tert-butyl-4-hydroxyphenyl)propane-1,2-dione dioxime and 3,5-di-tert-butyl-4-hydroxybenzohydrazide showed a high antioxidant efficiency in comparison to the known inhibitors 2,6-di-tertbutylphenol, 2,6-di-tert-butyl-4-mercaptophenol, and 2,6-di-tert-butyl-4-methylphenol (BHT), in model nonenzymatic human erythrocyte membrane lipid peroxidation.

Metal-based drugs are gaining momentum as a rapidly developing area of medicinal inorganic chemistry. Among gold pharmaceuticals, auranofin is a well known antirheumatic drug. The efficacy of gold-organic complexes largely depends on their pro-oxidant properties since auranofin targets the redox enzyme thioredoxin reductase (TrxR). However, an uncontrollable oxygen burst may be harmful for healthy cells; therefore, the search for chemical modifications to attenuate oxidation-related general toxicity of gold containing anti-inflammatory drugs is justified. In this study, we demonstrate that the incorporation of a specific antioxidant phenol fragment can counterbalance the pro-oxidative potential of the Au containing complex molecule. The electrochemical studies of AuPPh3SR (1, R= 3,5-di-tert-butyl-4-hydroxyphenyl) and its precursors AuPPh3Cl (2) and RSH (3) showed that complex 1 and phenol 3 efficiently scavenged the radicals (as detected by cyclic voltammetry) whereas 2 had no effect. Compound 1 inhibited TrxR in vitro with IC50 0.57 ± 0.15 μM, a value one order of magnitude bigger than the potency reported for auranofin. Compound 1 (5 mg kg-1 daily gavage for 14 days) caused a decrease in ex vivo spontaneous and ascorbate-induced lipid peroxidation in the homogenates of rat lung, heart muscle, spleen, liver, kidneys, testicles and brain as assessed by the thiobarbituric acid reactive substances. Importantly, in animals fed with 1, no discernible general toxicity was registered suggesting that this compound is well tolerated. Our results provide evidence for an efficient synthetic route to obtain gold containing anti-inflammatory drug candidates with balanced pro/anti-oxidative properties.

Polysubstituted derivatives of sterically hindered phenol were found to reduce accumulation of hydroperoxides in the lipid extract from fish feed after 8-week incubation. Feeding of juvenile Russian sturgeon with fish food containing these compounds showed no negative effect on hydrobionts. Both in vivo and in vitro experiments revealed inhibition of hepatic lipid oxidation in juvenile Russian sturgeon in the presence of new bis-pyrrolidine derivatives of 2,6-di-tert-butylphenol. A reliable positive correlation was observed between the concentration of hydroperoxides in the lipid extract from fish feed and accumulation level of secondary enzymatic oxidation products of hepatic lipids in hydrobionts.

Heterocyclic derivatives of butylated hydroxytoluene (BHT) were studied as cryoprotectants of the basic media for cryopreservation of the Russian sturgeon sperm. Rates of lipid peroxidation of sturgeon sperm before and after cryopreservation were reduced in the presence of the studied compounds, exceeding the effects of BHT and water-soluble analogue of vitamin E, trolox. The most efficient antioxidant has the effective concentration of 0.1 mM. Novel antioxidant agents as cryomedium supplements not only reduced the level of lipid peroxidation, but also enhanced the translational motility of the sperm of the Russian sturgeon after defrosting.

The effects of triphenylantimony(V) catecholate Ph3Sb(Cat) (1) and its spiroendoperoxide Ph3Sb(L-O2) (2) (Cat = 3,6-di-tert-butyl-4,5-dimethoxycatecholate) on lipid peroxidation (LP) in vitro and in vivo were examined in BALB/c line mice. A comparative study of the impact of compounds 1 and 2 on LP under similar conditions was made by measuring the formation of thiobarbituric acid reactive substances (TBARS). The anti- or pro-oxidant action of complexes 1 and 2 may be caused by the different redox level of the ligand acting as radical scavenger and/or by the bound molecular oxygen promoting the oxidation process. Biological experiments (in vitro and in vivo) were performed using mouse tissue homogenates. Decreasing TBARS concentration was observed in all examined tissues and blood serum (in vitro as well as in vivo) for catecholate 1. These results indicate inhibition of LP in the presence of complex 1. In contrast to 1, spiroendoperoxide 2 increases the level of TBARS in tissue homogenates. Minor fluctuations of TBARS concentration in erythrocytes and in blood serum indicate the absence of an obvious anti/pro-oxidant influence of 2 on the LP process in vivo. The role of catecholate fragment was found to be essential in explaining antioxidant properties. Copyright © 2014 John Wiley & Sons, Ltd.

ISSN 00125008, Doklady Chemistry, 2013, Vol. 451, Part 1, pp. 177–180. © Pleiades Publishing, Ltd., 2013.Original Russian Text © E.M. Mukh atova, V.P. Osipova, M.N. Kolyad a, N.O. Movchan, D.B. Shpakovsky, Yu.A. Gracheva, S.I. Orlova, E.R. Milaeva, 2013, published in DokladyAkademii Nauk, 2013, Vol. 451, No. 1, pp. 46–49.

A number of catecholates (complexes 1–3, 6) and o-amidophenolates (complexes 4, 5) of triphenylantimony(V) was examined in the process of lipid peroxidation of liver homogenates and sperm of Russian sturgeon (Acipenser gueldenstaedti B.), and human red blood cells. It was shown that the influence of complexes 1–6 on lipid peroxidation process in model systems depends on the nature of redox-active ligand and varies from weak anti- and pro-oxidant (catecholates 1, 6) to pronounced antioxidant (catecholates and o-amidophenolates 2–5). It was found that the complexes 2–5 are the more effective inhibitors of lipid peroxidation than standard antioxidant ionol. Copyright © 2012 John Wiley & Sons, Ltd.

The method of cyclic voltammetry on a platinum electrode in acetonitrile is used to study the redox properties of a number of novel pyrrolidine derivatives containing a sterically hindered phenol fragment. It is found that the obtained derivatives of (3,5-di-tert-butyl-4-hydroxyphenyl)pyrrolidine-2-carboxylic acid are irreversibly oxidized in two stages with formation of a phenoxy radical. The structural analogue containing no phenyl fragment is irreversibly oxidized under similar conditions in a single stage. Formation of a stable phenoxy radical from synthesized (3,5-di-tert-butyl-4-hydroxyphenyl)pyrrolidines under PbO2 oxidation is confirmed by ESR spectroscopy. Application of the synthesized compounds as antioxidant agents has been suggested.

The radical scavenging effect of the substituted catecholates (1–3, 6) and o-amidophenolates (4, 5) of triphenylantimony(V) in reactions with DPPH• radical and in a process of oleic acid peroxidation was studied in details. Complexes 1–6 show the high activity in radical scavenging reactions with DPPH• radical leading to disappearance of radical species. Complexes were demonstrated to be high-efficient inhibitors of chain-radical process of the peroxidation of oleic acid as well as the effective destructors of the formed hydroperoxides. It was found that the effectiveness of complexes studied in the inhibition of the peroxidation of oleic acid depends on the first oxidation potential of complex.

A cryoprotective effect of an addition of a new synthetic antioxidant – a representative of phosphorus-containing sterically hindered phenols is presented. The efficiency of the compound was shown to exceed the effect of lipid-soluble antioxidants butylated hydroxytoluene (BHT) and trolox in the conditions of cryopreservation of beluga sperm in the presence of the modified Stein’s medium. It was shown that the level of carbonyl oxidation by-products, which can react with thiobarbituric acid (TBARS), in beluga sperm was inversely proportional to the motility time of sperm cells. The fertility of beluga sperm increased 2 times upon the addition of phosphorus-containing phenol to a modified Stein’s medium. The prospects of the new antioxidant application to improve cryoresistance of beluga sperm in the conditions of cryopreservation for its efficient protection from the peroxidation processes are discussed.

A series of organotin complexes with Sn-S bonds of formulae Me2Sn(SR)2 (1); Et2Sn(SR)2 (2); (n-Bu)2Sn(SR)2 (3); Ph2Sn(SR)2 (4); R2Sn(SR)2 (5); Me3SnSR (6); Ph3SnSR (7) (R = 3,5-di-tert-butyl-4-hydroxyphenyl) were synthesized and characterized by elemental analysis, (1)H, (13)C NMR, and IR. The crystal structures of compounds 1, 4, 5, and 7 were determined by X-ray diffraction analysis. The tetrahedral geometry around the Sn center in the monocrystals of 1, 4, 5, and 7 was confirmed by X-ray crystallography. The high radical scavenging activity of the complexes was confirmed spectrophotometrically in a DPPH-test. The binding affinity of 1-7 and the starting R2SnCl2 (8) towards tubulin through their interaction with SH groups of proteins was studied. It was found that the hindered organotin complexes could interact with the colchicine site of tubulin, which makes them promising antimitotic drugs. Compounds 1-8 were tested for their in vitro cytotoxicity against human breast (MCF-7) and human cervix (HeLa) adenocarcinoma cells. Complexes 1-8 were also tested against normal human fetal lung fibroblast cells (MRC-5). Complexes 2-4 and 8 exhibit significantly lower cytostatic activity against the normal MRC-5 cell line compared to the tumor cell lines MCF-7 and HeLa used. A high activity against both cell lines 250 nM (MCF-7) and 160 nM (HeLa) was determined for the triphenyltin complex 7 while the introduction of hindered phenol groups decreases the cytotoxicity of the complexes against normal cells.

ISSN 00125008, Doklady Chemistry, 2010, Vol. 432, Pa rt 2, pp. 165–167. © Pleiades Publishing, Ltd., 2010.Original Russian Text © N.A. Antonova, V.P. Osipova, M.N. Kolyada, I.V. Smolyaninov, N.T. Berberova, V.Yu. Tyurin, Wu Yaohuang, E.R. Milaeva, 2010, published in DokladyAkademii Nauk, 2010, Vol. 432, No. 5, pp. 629–631.

This syndrome in newborns is insufficiently studied. The first descriptions of it appeared in 1949. The English doctor Mills (1949) observed 8 newborns with this pathology. The labor was long, all the children were born in asphyxia, and all were injected into the umbilical cord vessels immediately after birth with nekelmamide, a synthetic drug that excites the respiratory center and the cardiovascular system. According to Mills, paralysis and circulatory disorders are associated with thrombosis of the inferior episodic artery, which feeds the sciatic nerve and the corresponding area of the skin of the gluteal region. Later, similar cases were described by Hudson and co-authors, San Augustine, T. N. Dorofeeva, V. L. Zubkova and V. A. Tabolin.