Novel derivatives of 3-[3,5-dioxy-1,2,4,5-tetrahydro-1,2,4-triazinyl-6]-propionic acid: synthesis and antifungal effect

V.G. Коstіnа¹, I.V. Alexeeva¹, N.A. Lysenko¹, S.M. Grigorjeva², D.Р. Egorov², S.L. Rybalko², A.D. Shved¹

¹ Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Zabolotnogo Str., Kyiv, 03680, Ukraine

² SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases of AMS Ukraine»
5, Amosova Str., Кyiv, 03038, Ukraine

Summary. Series of novel aryl- and pyridinylamides of 3-[3,5-dioxy-1,2,4,5-tetrahydro-1,2,4-triazinyl-6]-propionic acid (TPA) was synthesized. A series of hybrid compounds of 2-[3,5-dioxy-1,2,4,5-tetrahydro-1,2,4-triazinyl-6]-ethyl-benzimidazol, -thiazol, -oxazol was produced via condensation of TPA in presence of polyphosphoric acid with appropriate o-amino-, o-mercapto- and o-hydroxy-аminobenzenes. Anticandidosis activity was found for 10 TPA arylamides within the range between 25.0 and 12.5 mkg/ml. Three arylamides, 7, 8 & 15, displayed fungicide effect for two Candida albicans strains upon inoculate loading of 1х10⁷ cells per 1.0 ml. The results obtained suggest the prospects of the compounds involved for further studies.

Keywords: arylamides of 3-[3,5-dioxy-1,2,4,5-tetrahydro-1,2,4-triazinyl-6]-propionic acid, synthesis, antifungal activity, Candida albicans.

Molecular complex of the triterpene glycoside α-hederin and sildenafil citrate (viagra): FT-IR and UV spectroscopy analysis and biological activity

L.A. Yakovishin, D.Yu. Belash, I.R. Yarovoy

Sevastopol National Technical University
33, University Str., Sevastopol, 99053, Ukraine

Summary. Molecular complex of the triterpene glycoside α-hederin (hederagenin 3-O-α-L-rhamnopyranosyl-(1→2)-O-α-L-arabinopyranoside) with sildenafil citrate (viagra) has been prepared. The complexation has been confirmed by FT-IR and UV spectroscopy for the first time. The glycoside forms complex with sildenafil citrate in a 1:1 molar ratio. Intermolecular interaction has been accompanied by a hyperchromic effect. The ichtyotoxic activity of the molecular complex was investigated on Poecilia reticulata.

Keywords: triterpene glycosides, a-hederin, sildenafil citrate, molecular complex, UV spectroscopy, FT-IR spectroscopy, Poecilia reticulate, ichtyotoxic activity.

Synthesis and antioxidant activity of 6- and 7-hydroxy-3-arylcoumarins

S.P. Bondarenko¹, M.S. Frasinyuk², V.P. Khilya³, T.M. Panteleymonova⁴, I.S. Bezverkha⁴

¹ National University of Food Technologies
68, Volodymirska Str., Kyiv, 01601, Ukraine

² Institute of Bioorganic and Petroleum Chemistry, NAS of Ukraine
64, Murmanska Str., Kyiv, 02094, Ukraine

³ Taras Shevchenko Kiev National University
64, Volodymirska Str., Kyiv, 01033, Ukraine

⁴ SI «D.F. Cheborarev Institute of Gerontology NAMS of Ukraine»
67, Vyshgorodska Str., Kyiv, 04114, Ukraine

Summary. A number of substituted of 6- and 7-hydroxy-3-aryl coumarins were synthesized and tested for anti-oxidative activity in vitro. Some compounds were selected as promise for further preclinical investigation as antioxidant drugs by means of their biological research.

Keywords: 3-arylcoumarin, antioxidative activity, tween 80, malonaldehyde, 2-thiobarbituric acid.

Enzymatic method for L-arginine assay based on recombinant human arginase I

N.Ye. Stasyuk^1,2, G.Z. Gayda¹, A.V. Gayda¹, M.V. Gonchar¹, Ye.P. Koval’chuk²

¹ Institute of Cell Biology, NAS of Ukraine
14/16, Drahomanov Str., Lviv, 79005, Ukraine

² Ivan Franko National University of Lviv
6, Kyryla and Mefodia Str., Lviv, 79005, Ukraine

Summary. Enzymatic-spectrophotometric method for L-arginine assay based on human arginase I isolated from the recombinant yeast strain Hansenula polymorpha was developed. The new method is selective and rather simple. Linear detection range was estimated to be from 0.007 to 0.1 mМ in reaction mixture, and detection limit – 0.005 mM L-arginine. The method was tested on the real samples of L-arginine-containing commercial pharmaceuticals pro-ducts. It was shown, that the estimated L-arginine contents were in a good correlation with that declared by producers, with results of referent chemical (R=0.998) and some other methods.

Keywords: L-arginine, arginase I, enzymatic method, diacetyl-(2,3-butandione) monooxime.

The selection of descriptors for QSAR (quantitative structure-activity relationships) building using genetic algorithm and modified multiple-searching method

V.V. Markov¹, A.P. Boichenko², L.P. Loginova¹

¹ V.N. Karazin Kharkiv National University
4, Svobody Sq., 61022, Kharkiv, Ukraine

² Analytical Biochemistry, University Centre for Pharmacy
1, A. Deusinglaan, 9713, AV Groningen, The Netherlands

Summary. In this work on the basis of selected descriptors the quantitative relationships structure-partition constant in two phase systems chloroform – gas, chloroform – water, 1-octanol – water has been constructed. The search of descriptors has been done by using the exhaustive search and genetic algorithm. The optimization of algorithm parameters was done that allow to reduce the time of calculations. The relationships were constructed with and without using the group of molecular properties descriptors which are calculated on the basis of empirical models. The constructed relationships have high goodness-of-fit (the correlation coefficient is not lower than 0.92) and high predictive capacity.

Keywords: structure-property relationships, partition, descriptor, genetic algorithm.

Influence of drugs on physico-chemical parameters phospholipid monolayers as a model for determination of permeability compounds across biological membranes

A.M. Lyakhov, V.V. Kovalishin, V.V. Prokopenko

Institute of Bioorganic Сhemistry and Petrochemistry, NAS of Ukraine
1, Murmanska Str., Kyiv, 02094, Ukraine

Summary. The effect of drugs on physico-chemical parameters of the monolayer films made of distearoylphosphatidylcholine were studied. It is shown, that this properties can be used to predict the permeability of drugs through the blood-brain barrier and skin. Quantitative values of physico-chemical monolayer films parameters can be used to build more accurate computer models of permeability compounds across biological membranes.

Keywords: phospholipids monolayer films, distearoylphosphatidylcholine, drugs, permeability, biological membranes.

Inhibitors of protein kinase FGFR1 from phenylhydrazine class

A.A. Gryshchenko, V.G. Bdzhola, A.O. Balanda, S.S. Lukashov, I.M. Fesun, S.M. Yarmoluk

Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Zabolotnogo Str., Kyiv, 03680, Ukraine

Summary. Protein kinase FGFR1 plays a key role in oncogenic transformation and oncovasculogenesis. Inhibitors of this kinase can be used as anticancer drugs. In this work phenylhydrazines as inhibitors of protein kinase FGFR1 were investigated. Phenylhydrazines were found by virtual screening. The most active compound was 2-methoxy-4-[(5-trifluoromethyl-pyridin-2-yl)-hydrazonomethyl]-phenol with IC₅₀ 2,5 µM. Structure features of investigated compounds related to inhibition activity were defined.

Keywords: protein kinase FGFR1, phenylhydrazine, docking, inhibitor.

Vibrational spectra of sanguinarine and their interpretation by means of DFT quantum-mechanical calculations

N.V. Bashmakova¹, S.Yu. Kutovyy¹, R.O. Zhurakivsky², R.S. Savchuk¹, V.V. Strelchuk³, D.M. Hovorun^2,1

¹ National Taras Shevchenko University of Kyiv
64, Volodymyrska Str., Kyiv, 01601, Ukraine

² Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Zabolotnogo Str., Kyiv, 03680, Ukraine

³ V. Lashkaryov Institute of Semiconductor Physics, NAS of Ukraine
41, pr. Nauki,  Kyiv, 03028, Ukraine

Summary. Experimental vibrational spectra (Raman and infrared absorption) of microcrystalline sanguinarine chloride were obtained at room temperature. Calculated vibrational spectra were received within DFT B3LYP/6-311++G(d,p) theory level for iminium and alkanolamine forms. Based on correlation between experimental and calculated data the vibrational spectrum was interpreted in detail in the frequency range of 600-1700 sm^-1. Experimental and calculated spectra of intramolecular vibrations were found to be closely correlated.

Keywords: sanguinarine, vibrational spectra, DFT, DNA intercalators.

New 2-quinolinone derivatives: synthesis and CK2 inhibitor activity

А.R. Synyugin¹, M.O. Chekanov¹, O.Yu. Nyporko^2,1, O.V. Ostrynska¹, S.M. Yarmoluk¹

¹ Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Zabolotnogo Str., Kyiv, 03680, Ukraine

² Taras Shevchenko Kyiv National University
60, Volodymirska Str., Kyiv, 01601, Ukraine

Summary. In this work virtual screening of generated combinatorial library of 7786 2-quinolinone derivatives was carried out. 98 compounds of this class were synthesized and characterized as potential human protein kinase CK2 inhibitors for the first time. None of synthesized compounds inhibit CK2 activity less than 40 % according to bioche-mical tests. The complexes of 2-quinolinone derivatives with CK2 were obtained by using molecular docking method. Compounds position in enzyme ATP-binding site and key interaction with its amino acid residues were analyzed. These compounds can be recommended for inhibitor activity studies at others enzymes.

Keywords: 2-quinolinone, human protein kinase CK2 inhibitor, virtual screening, 2-quinolinone-3-yl carbonic acid, 2-quinolone-6-acetic acid, combinatorial library.

Synthesis of hydrochloric acid salts of 2-pyrrolidine-4-aniline-6-arylamino-1,3,5-triazine derivatives and their activity towards Rhinovirus strain HGP on cells HELA OHIO-1

Yu.V. Renkas, V.A. Siryi

Institute of Pharmacology and Toxicology AMSU
14, Ezhena Potie Str., Kyiv, 01000, Ukraine

Summary. The article describes the methods of synthesis of hydrochloric acid salts of 2-pyrrolidine-4-aniline-6-arylamino-1,3,5-triazine, as well as data on their antiviral properties. Pharmacological in vitro studies conducted in the screening program National Institute of Health showed that these compounds have some activity towards Rhinovirus strain HGP on cells HELA OHIO-1. The data obtained activity show promise for further search of antiviral agents in a series of hydrochloric acid salts of 2-pyrrolidine-4-aniline-6-arylamino-1,3,5-triazine.

Keywords: 1,3,5-triazine, 2-pyrrolidin-4-aniline-6-arylamino-1,3,5-triazine, Rhinovirus strain HGP, cells HELA OHIO-1.