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Information × Registration Number 0218U000739, 0115U000763 , R & D reports Title New biologically active compounds, methods of synthesis, physico-chemical and biological properties popup.stage_title Head Omelyanchik Lyudmila Aleksandrovna, Registration Date 12-02-2018 Organization Zaporozhye National University popup.description2 The object of the study is biologically active substances on the basis of S-heteryl substituted endogenous sulfur-containing compounds. The purpose of the work is to create new effective bioregulators among S-derivatives of endogenous sulfur-containing compounds and their analogues, to establish a relationship between chemical structure and biological action, and to study the mechanisms of action of the most active substances. Study the effect of carboxyl and amine groups' presence or absence on the manifestation of biological activity in the cysteine molecule S-derivatives of endogenous sulfur-containing compounds. Research methods and equipment. Virtual screening (PASS-forecast, QSAR-analysis), chemical synthesis, methods of chemoinformatics and laboratory synthesis of organic substances, physical and chemical methods (elemental analysis, thin-layer chromatography, IR, PMR-chromatography, mass spectrometry), biological, biochemical and statistical methods. The following research methods have been used in research work: computer forecasting, methods of chemoinformatics and laboratory synthesis of organic substances, physical and chemical methods (elemental analysis, thin-layer chromatography, IR, PMR, chromatography, mass spectrometry), biological and biochemical methods (research of antioxidant activity, toxic, antibacterial, rostistymigating, nootropic, antidepressant, antihypoxic and neuroprotective action). PASS prognosis and QSAR analysis were performed using well-known PASS, MOPAC, JSDraw, OpenBabel, PaDEL-Descriptor, McQSAR, Pandoc, and developed and tested in the laboratory of biotechnology at the Faculty of Biology of the ZNU computer program QuS. Statistical processing of the results was carried out using a package of standard computer programs. Methods were used: IR spectra were recorded on the Bruker ALPHA FT-IR spectrometer on the ATR; The chromatic-mass spectra were taken on the device "AGILENT 1100"; Elemental analysis of the compounds was performed using ELEMENTAR vario EL cube elemental analyzer; The spectra of the PMR were taken on the Bruker AC-300 (300 MHz) device in DMSO-d6 + CCl4 (1: 1), the internal standard TMS; thin-layer chromatography was carried out on plates of "Silufol UV" of the Slovak production in various solvent systems; the determination of the melting point was carried out in accordance with the requirements of the SPF; The lipophilicity of the compounds was determined by the method of "shaking" and extraction of a substance from butanol (concentration 10 -4 mol / l) with an aqueous phase (ratio of volumes of the aqueous phase and butanol Vw: Vbut = 5: 1); ionization constants (pKa) were determined by pH-metric method at pH-meter -150 MA. Acute toxicity was studied using the table express method for Prozorovsky VB; evaluation of antioxidant activity in vitro by inhibition of autocoxification of adrenaline, by inhibition of the NO-radical, by inhibition of the oxidative modification of the protein, by inhibition of "nitrogen-stimulating stress; antimicrobial activity was studied by serial dilutions; cytotoxicity was evaluated at root cucumber spp. Cucumis sp .; nootropic activity on the "open field" model; antidepressant activity was assessed using the Porsolt test; antihypoxic action was determined on the model of gemic hypoxia; Biochemical studies of SOD activity, catalase, glutathione peroxidase, and oxidizing modification of proteins were performed according to standard biochemical methods; Statistical processing of data was carried out using a standard package of computer programs MS Excell. Used equipment: Saturn-3-P1 atomic absorption spectrophotometer, Laboratory IDC-M deformation gauge, UV-spectrophotometer SF-46; Spekol-211; microspectrom fl uarimeter MSF-2; luminescent microscope ML-2; biological microscope Biolam P2; photoelectrocolorimeter KFK-2; pH meter "РН-340"; pH meter 150MA; centrifuge TSLU-1; analytical weights WDR-1; refractometer RL-3; centrifuge MPW-310; vacuum drying cabinet SPT-200; gas chromatograph Model 3700-0.1; bath bacteriological tuberculosis; magnetic stirrer MM6, volt ammetric analyzer with TA-1 UV irradiation, chemical and biological utensils and reagents for study, animals - mice of bovine species weighing 16-22 g, and white rats of the Vitast line weighing 220-260 g from the kennel of the Institute of Pharmacology and toxicology of the Academy of Medical Sciences of Ukraine (Kyiv).Using virtual screening and QSAR analysis, an effective strategy for the purposeful search for biologically active substances has been developed, combining bioorganic chemistry approaches with in vitro and in vivo biological research, within which was synthesized a number of new S heteryl derivatives of endogenous sulfur-containing compounds and their functional substitutions (more than 40 new biologically active compounds with confirmed structure). Based on the biological research in vitro and in vivo, the structural-biological patterns of these molecular systems were established. Was discovered effective antioxidative agent, 3- (2-methyl-5,8-dimethoxyquinoline-4-ilthio) propanoic acid, a promising neurometabolic antioxidant and cerebroprotector, disodium salt of 2- (2-methyl-5,8-dimethoxyquinolin-4-ilthio) succinic acid. For this substance was developed preparative method of synthesis, a method of quantitative analysis using ion-selective electrodes and was studied specific activity . For the first time were studied nootropic and antihypoxic effects of a non-toxic compound - the disodium salt of 2-(pyridine-4-ilthio) succinic acid. The results of research allow us to recommend it as a promising substance for the creation of a nootropic agent. The results of the work were introduced into the scientific research process of a number of higher educational institutions of Ukraine and used in the scientific-research and production processes of the clinical and biochemical laboratory of "SE ZMDB Ivchenko-Progress", Institute of Oilseeds of NAAS of Ukraine. Product Description popup.authors Євлаш Аліна Сергіївна Єщенко Юлія Віталіївна Борисенко Данило Романович Бражко Олександр Анатолійович Бражко Олена Олександрівна Веселков Артем Володимирович Генчева Вікторія Іванівна Гороховський Євген Юрійович Завгородній Владислав Михайлович Завгородній Михайло Петрович Карпенко Юрій Вікторович Кириченко Владислав Ігоревич Корнет Марина Миколаївна Лабенська Ірина Борисівна Лагрон Аліса Вадимівна Луганська Ольга Василіївна Омельянчик Людмила Олександрівна Панасенко Тамара Володимирівна Петруша Юлія Юріївна Синяєва Ніна Петрівна popup.nrat_date 2020-04-02 Close