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2010 Vol VIIІ #1


The novel physico-chemical mechanism of the Watson-Crick base pair Ade·Thy transformation to the mispairs involving mutagenic tautomers Ade*·Thy and Ade·Thy*

O.O. Brovarets'1,2, D.M. Hovorun2,1

1 Institute of High Technologies of Taras Shevchenko Kyiv National University
2 Hlushkova Ave., Kyiv, 03187, Ukraine

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

Summary. On the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory it is established the new physicо-chemical mechanism of the transformation of watson-crick base pair Ade·Thy to the mispairs formed by the rare tautomers (designated by the asterisk) Ade*·Thy and Ade·Thy* through the same transition state as ion pair Ade+·Thy- with the Gibbs energy of activation 17.38 kcal/mol which is stabilized by four hydrogen bonds N6H…O4, N6H…N3-, N1+H…N3- and N1+H…O2. Stable pairs Ade*·Thy and Ade·Thy* have acceptable relative Gibbs free energy and dissociation (9.94 and 12.43 kcal/mol and 6.06 and 1.61 kcal/mol accordingly) for the explanation of spontaneous point DNA replication errors arising.

Keywords: spontaneous point DNA replication errors, transitions, mutagenic tautomers of DNA bases, mispairs, transition state, intermolecular hydrogen bonds, analysis of the electron density topology, DFT.

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Molecular mechanisms of 2-aminopurine mutagenic influence on DNA

O.O. Brovarets'1,2, D.M. Hovorun2,1

1 Institute of High Technologies of Taras Shevchenko Kyiv National University
2 Hlushkova Ave., Kyiv, 03187, Ukraine

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

Summary. It is established for the first time on the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory that 2AmPur-induced replication errors realize in a way 2AmPur·Thy2AmPur·Thy*, herewith 2AmPur·Thy* population exceeds Ade·Thy* population which defines spontaneous mutagenesis ~1390 times under standard conditions. It is proved that replication errors frequencies induced by 2AmPur exceed on a few degrees incorporation errors frequencies in the 2AmPur·Cyt2AmPur·Cyt* pathway. For the first time it is established that hypothetical ionization mechanism of mutagenic action of 2AmPur is non-adequate.

Keywords: 2-aminopurine, point mutagenesis, replication errors, incorporation errors, ionization mechanism, transitions, DNA base mispairs, transition state, intermolecular hydrogen bonds, analysis of the electron density topology, DFT.

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Influence of deprotonated carboxylic group and sodium ion on tautomeric equilibrium of xanthine and
hypoxanthine: spectroscopic and quantum chemical data

O.O. Brovarets'2,1, S.P. Samijlenko1, A.V. Stepanyugin2, D.M. Hovorun2,1

1 Institute of High Technologies of Taras Shevchenko Kyiv National University
2 Hlushkova Ave., Kyiv, 03187, Ukraine

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

Summary. Using UV, IR and 1Н NMR spectroscopy, hypoxanthine (Hyp) and xanthine (Xan) complex formation with sodium acetate (NaAc) was established in anhydrous dimethylsulfoxide (DMSO) at room temperature. It was shown that formation of these complexes results in significant changes in UV spectra, vanishing of all signals of imino protons (two for Hyp and three for Xan) in 1Н NMR spectra and redistribution of the IR bands intensities of valence carbonyl vibrations in IR spectra. By means of quantum-chemical calculations at the MP2/6-311++G(2df,pd)// B3LYP/6-311++G(d,p) level of theory and using polarization continuum model (PCM) experimental data was eplained based on the analysis of the all possible triple complexes like Na+·base tautomer·CH3COO- stabilized by two H-bonds. Vanishing of the imino proton signals 1Н NMR spectra can be explained by coexistence of the complexes where imino protons form strong H-bonds and perturbation of IR spectra can be explained by enolization of the bases in these complexes and interaction of Na+ ion with oxygen atom of carbonyl group within them.

Keywords: xanthine, hypoxanthine, UV, 1Н NMR and IR spectroscopy, tautomerization, quantum chemistry.

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Molecular complex’s formation of the triterpene glycoside α-hederin with caffeine in aqueous solution

L.A. Yakovishin

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

Summary. For the first time molecular complex of the triterpene glycoside α-hederin (3-O-α-L-rhamnopyranosyl-(12)-O-α-L-arabinopyranoside of hederagenin) with caffeine in aqueous solution is received. The complex’s formation is confirmed by UV-spectroscopy. Established that the complex includes two molecules of α-hederin and a molecule of caffeine. The molluscicidal activity of α-hederin, caffeine and their complex was investigated on Planorbis corneus.

Keywords: triterpene glycosides,
α-hederin, caffeine, molecular complex, clathrate, UV-spectroscopy, Planorbis corneus, molluscicidal activity.

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N-(2-Aryl-4-thiocarbamoyl-1,3-oxazol-5-yl)-β-alanine — specific inhibitors of CK2 protein kinase

O.V. Shablykin1, O.P. Kozachenko1, V.S. Brovarets1, O.V. Ostrynska2, O.P. Kucharenko2, I.B. Labenskaya3, L.A. Omelyanchik3, S.M. Yarmoluk2

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

2 Institiute of Molecular Biology and GeneticS NAS of Ukraine
150 Zabolotny Str., Kyiv, 03680, Ukraine

3 Zaporizhzhya National University
66 Zhukovskogo Str., Zaporizhzhya, 63000, Ukraine

Summary. We have studied the interaction of newly synthesized N-(2-aryl-4-thiocarbamoyl-1,3-oxazol-5-yl)-β-alanine with CK2 protein kinase. The influence of substituents in position of the 2 oxazole for their activity is considered. The binding mode of inhibitors with enzyme was predicted by molecular docking of compounds in the ATP pocket of CK2 protein. The selectivity of CK2 inhibition was revised by in vitro tests on some other protein kinases. For the most active compound the common toxicity was established.

Keywords: protein kinase CK2, N-(2-aryl-4-thiocarbamoyl-1,3-oxazol-5-yl)-
β-alanine, inhibitors, docking.

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Influence of aza-15-crown-5 with nootropic activity on protein metabolism in various regions of rats brain and blood

Т.L. Каraseva, G.N. Zapenko, S.S. Basok, K.Yu. Kulygina, N.G. Luk’yanenko

A.V. Bogatsky Physico-Сhemical Institute of National Academy of Sciences of Ukraine
Lustdorfskay doroga, 86, Odessa, 65080, Ukraine

Summary. The influence of crown-ether (CE), possessing nootropic activity on the protein metabolism in various structures of mice brain and rats blood in comparison with piracetam were studied. It was found, that CE was able to increase the protein content, to activate the synthesis of total protein and its fractions in different regions of brain. The distinct inclusion of 3H-leicin and 35S-methionine in total content of blood proteins were found.

Keywords: piracetam, N-(γ-аminobutyryl)aza-15-crown-5, proteins of blood and brain, nootropic activity.

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Antitumor activity of 1-benzyl-3-chloro-4-amino-1H-pyrrole-2,5-dione derivatives

S.S. Tarnavskiy, O.P. Kukharenko, N.V. Briukhovetska, V.M. Kharchenko, S.M. Yarmoluk

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

Summary. Forty derivatives of the 1-benzyl-4-anilino-2,5-dihydro-1H-2,5-pyrroledione were synthesized and tested for antitumor activity in vitro. According to the results of pre-screening included three human tumor cell lines fifteen compounds were shown to inhibit proliferation of cancer cells. These compounds were proceeded to testing on 64 human tumor cell lines. The 3-chloro-1-(4-chlorobenzyl)-4-[(3-chlorophenyl)amino]-1H-pyrrole-2,5-dion and 3-chloro-1-(4-chlorobenzyl)-4-{[(3-trifluoromethyl)phenyl]amino}-1H-pyrrole-2,5-dione inhibited the growth of tumor cells (GI50=1·10-8-4,4·10-6 М).

Keywords: maleimide derivatives, human tumor cell lines, antitumor activity.

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The model of photoinduced changes in the pigment-protein complex of reaction center

М. Zabolotny1, Yu. Barabash2, Yu. Sklarov3, Yu. Prilutsky1

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

2 Institute of Physics of NASU
46, Nauki av., Kyiv, 03650, Ukraine

3 Bogomolets National Medical University
13, Shevchenko blv., Kyiv, 01601, Ukraine

Summary. The slow dynamics of isolated complexes of the chlorophyll containing membrane proteins in photosynthetic reaction centers (RCs) in Rb. sphaeroides R-26 which is induced by light flows has been studied experimentally. The changes of the RC solution absorption have been analyzed theoretically in terms of the three-level model. The equation that has been obtained determines the ratio between the population of electron levels of the primary and secondary chinons. The solution of this equation even for stationary case has been found to bear non-Boltshman character and depend on the intensity of the excitation light. The suggested model of level dynamics in RCs takes into account the probability of polarization processes in the vicinity of the secondary chinon QB in the result of numerous photoinduced electron transitions. All the RCs are assumed to have identical structural deformation but may be in different states whose characteristics depend on time duration after light quantum absorption as well as on viscosity and elasticity of the QB surrounding.

Keywords: reaction center, photoinduced electron transition, theoretical model.

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Amino acid derivatives of 6,7-N-substituted 1,4-naphthoquinone and investigation of their influence on embryo morphology of loach during embryogenesis

I. Buchkevych, O. Yaremkevych, O. Figurka, O. Stanko, M. Stasevych, R. Musyanovych,V. Novikov

National University «Lviv Polytechnic»
12, Bandera Str., Lviv-13, 79013, Ukraine

Summary. The synthesis of order of new 7-nitro-6-amino acid derivatives of substituted 1,4-naphthoquinone was carried out for the first time. It was found that in an order of the synthesized compounds there are substances which cause the growth inhibition and development of embryos of Misqurnus fossilis L., that is ponderable reason for subsequent investigations for antitumor activity.

Keywords: amino acide, naphthoquinone, Misqurnus fossilis L. embryos, morphology, embryotoxicity.

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Synthesis of new 2-amino-3-hetaryl-5H-[1]benzopyrano[2,3-b]pyridine-5-one derivatives

A.V. Borovikov, V.M. Sapelkin, A.O. Prykhod'ko, S.M. Yarmoluk

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

Summary. In order to decrease the limits of the reaction application and synthesis of new 5H-[1]benzopyrano[2,3-b]pyridine-5-one derivatives reaction of 3-cyanobenzopyrane-4-ones and heterylacetonitriles has been studied. This reaction leads to expected 2-amino-3-hetaryl-5H-[1]benzopyrano[2,3-b]pyridine-5-one derivatives. Thus, new synthetic route to rare 2-amino-3-hetaryl-5H-[1]benzopyrano[2,3-b]pyridine-5-one derivatives has been developed.

Keywords: 2-amino-3-hetaryl-5H-[1]benzopyrano[2,3-b]pyridine-5-ones, 3-cyanobenzopyrane-4-ones, heteryl-acetonitriles.

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Synthesis and some properties of vicinal 2-(pyridin-3-yl)-2-[aryl(hetaryl)-sulfonyl]-ethanamines

O.V. Rudnichenko, I.M. Fesun, А.R. Synyugin, M.O. Chekanov, I.M. Kotey, S.M. Yarmoluk

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

Summary. As a part of study on the synthesis of sulfur-containing compounds of pharmacological interest, 2-aryl(hetaryl)-2-[aryl(hetaryl)-sulfonyl]-nitroethanes were prepared by the reaction of aryl- and hetarylaldehydes with nitromethane in the condition of Henry condensation, and the subsequent addition of a sulfinic acids. There are row of a new 2-(pyrid-3-yl)-2-[aryl(hetaryl)-sulfonyl]-ethanamines were synthesized as an Thymidylate synthase inhibitor analogue. Number of a corresponding amides and sulfonamides was obtained by the acylation and sulfonylation reactions.

Keywords: pyridin-3-carboxaldehyde, N-(2-(arylsulfonyl)-2-(pyrid-3-yl)-ethan)-amides, N-(2-(arylsulfonyl)-2-(pyrid-3-yl)-ethan)-sulfonamides, antagonists, vic-aminosulfones.


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