Feature of aminomethylation of esculetin derivatives

M.S. Frasinyuk

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

Summary. 4-Subsituted esculetinederivatives were synthesized by condensation of pyrogalol A ethyl acetoacetate orethyl 4-chloroacetoacetate under Pechmann’s reaction. 4-Hydroxymethylesculetin was synthesized by acetylation of 4-chloromethylesculetin with acetic anhydride in presence of potassium acetate and subsequent deacylation in ethanol. Aminomethylation of 4-methyl- and 4-hydroxymethyl esculetin derivatives was studied at various reaction conditions. A different 8-aminomethyl esculetine derivatives and 2H,8H-chromeno[8,7-e][1,3]oxazin-2-ones were synthesized with good or excellent yield.

Keywords: Pechmann’s reaction, esculetine, Mannichbase.

The complete family of H-bonded DNA base pairs m¹Thy·m¹Thy. Quantum chemical study

D.P. Plodnik¹, I.S. Voiteshenko^1,2, D.M. Hovorun<sup>1,2

1</sup> Institute of High Technologies, Taras Shevchenko National University of Kyiv
2g, Hlushkova Ave, Kyiv, 03022, Ukraine

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

Summary. For the first time at MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory by a quantum-chemical methods was received a complete family of H-linked self associates of nucleotide bases m¹Thy·m¹Thy, which includes 10 different structures. An intermolecular hydrogen bonds that stabilize them was described; the main attention is paid to hydrogen bonds CH...N.

Keywords: thymine, self association, hydrogen bonds, quantum chemistry.

Synthesis and study of inhibitory activity against the protein kinase CK2 in a series of derivatives of imidazo[1,5-a]pyridine

D.O. Tverdiy¹, P.V. Savytskyi², M.O. Chekanov², A.R. Synyugin², P.D. Medic², R.V. Chepurna², S.M. Yarmoluk²

¹ National Technical University of Ukraine «Kyiv Polytechnic Institute»
37, Peremohy Ave., Kyiv, 03056, Ukraine

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

Summary. Fifteen imidazo[1,5-a]pyridine derivatives were synthesized and their testing in vitro on the ability to inhibit protein kinase CK2 was conducted. Two compounds with residual activity values of 40 and 60 % respectively were discovered. That indicates the advisability of further search of effective inhibitors of protein kinase CK2 in a series of derivatives of imidazo[1,5-a]pyridine.

Keywords: imidazo[1,5-a]pyridine, protein kinase CK2, inhibitor.

Discovery of novel protein kinase FGFR1 inhibitors using pharmacophore modeling

S.A. Starosyla, G.P. Volynets, M.V. Protopopov, V.G. Bdzhola, S.V. Dzyadevych, O.V. Borovykov, L.V. Pletnyova, S.M. Yarmoluk

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

Summary. Protein kinase FGFR1 plays important roles in cell proliferation, angiogenesis, migration, and survival. Increased activity of FGFR1 is associated with several malignancies and disorders. FGFR1 has been proved to be attractive molecular target for therapeutic intervention in cancer, and it is high interest to design FGFR1 inhibitors with novel chemical scaffolds. We have developed receptor-based pharmacophore model of FGFR1 inhibitors and performed pharmacophore screening which allowed us to identify two novel classes of FGFR1 inhibitors — the derivatives of 3-(1-benzyl-1H-indol-3-yl)-2-cyanoacrylic acid and N-[(phenylmethylidene)amino]thiourea and several hit compounds.

Keywords: protein kinase FGFR1, pharmacophore model, inhibitor.

Recent progress in the development of protein kinase CK2 inhibitors

A.O. Prykhod'ko, G.P. Volynets, V.G. Bdzhola, S.M. Yarmoluk

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

Summary. Protein kinase СК2 is ubiquitous and highly pleiotropic protein kinase, implicated in several human diseases. This paper presents an overview of the published data concerning the role of CK2 in oncogenesis and in progression of viral infections and neurodegenerative diseases. Also, we report chemical classes of CK2 inhibitors available in literature and analyze their efficiency in vitro and in vivo.

Keywords: protein kinase CK2, oncogenesis, viral infections, neurodegenerative diseases, inhibitor.

Investigation of inhibitory activity of imidazolone derivatives and their precursors toward human protein kinase CK2

V.M. Naumchuk, G.P. Volynets, O.B. Gorbatiuk, S.S. Lukashov, V.G. Bdzhola, S.M. Yarmoluk

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

Summary. We have investigated inhibitory activity of imidazolone derivatives and their precursors toward protein
kinase CK2. As a result, we have found seven inhibitors with ІС₅₀ values in the range from 8 to 30 µМ.

Keywords: imidazolones, protein kinase CK2, inhibitor.

The synthesis of combinatorial row of aurone derivatives as potential inhibitors of protein kinase CK2

V.S. Vdovin, S.S. Lukashov, I.P. Borysenko, I.M. Fesun, S.M. Yarmoluk

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

Summary. The series of halo-substituted cumaranone-3 derivatives was synthesized using base induced cyclization of ortho-hydroxy-chloroacetophenones. Novel aurone derivatines were obtained by the condensation of halo-cumaranones-3 and aldehydes with the yields in a range of 15-90 %.

Keywords: aurones, cumaranones, protein kinase CK2, inhibitor.

The population of Ukraine is poisoned with toxic water!

Viktoriia V. Lipson

Sergiy I. Okovytyy