[22] Synthesis and structural study of N-substituted-1,7-dithia-4-azaspiro[4.4]nonan-3-one 7,7-dioxides
P.V. Shaitanov, S.S. Lukashov, O.V. Turov, S.M. Yarmoluk
Ukrainica Bioorganica Acta. – 2007. – Vol. 5, No. 2. – Ñ. 56-61 (in Ukraine).Abstract
Reaction of 3-bromo-2,3-dihydrothiophene 1,1-dioxide with N-substituted-2-mercapto-N-R-acetamides in presence of KOH gave new derivatives of 1,7-dithia-4-azaspiro[4.4]nonane heterocyclic system. Structure of obtained derivatives was confirmed by methods of NÌR-spectroscopy.
[21] Synthesis of 4-substituted 1-arylhexahydrothieno[3,4-b]pyrazin-2(1H)-one 6,6-dioxides
P.V. Shaitanov, Yu.V. Bezugly, V.M. Sapelkin, S.M. Yarmoluk
Ukrainica Bioorganica Acta. – 2006. – Vol. 4, No. 2. – Ñ. 40-46 (in Ukraine).Abstract
An effective method of synthesis of 4-substituted 1-arylhexahydrothieno[3,4-b]pyrazin-2(1H)-one 6,6-dioxidesis on the basis of 3-arylamino-2,3-dihydrothieno 1,1-dioxides is proposed. The biological activity of new bicycle sulfones has been predicted using PASS software.
[20] Synthesis and structural characteristics of 4-(2-phenylethyl)-1,7-dithia-4-azaspiro[4.4]nonan-3-one 7,7-dioxide
P.V. Shaitanov, Yu.V. Bezugly, V.M. Charchenko, S.M. Lukashov, S.M. Yarmoluk
Ukrainica Bioorganica Acta. – 2005. – Vol. 3, No. 2. – P. 39-42 (in Ukraine).Abstract
4-(2-phenylethyl)-1,7-dithia-4-azaspiro[4.4]nonan-3-one 7,7-dioxide, the derivative of new heterocyclic system 1,7-dithia-4-azaspiro[4.4]nonane, was obtained by interaction of 3-bromo-2,3-dihydrothiophene 1,1-dioxide with 2-mercapto-N-(2-phenethyl)-acetamide in the presence of the KOH in the alcohol solution. Its structure was proven with X-ray spectroscopy.
[19] Synthesis of 7-(3-dialkylamino-2-hydroxypropoxy)-3-aryloxychromones
A.O. Prykhodko, S.P. Kobzev, S.M. Yarmoluk
Ukrainica Bioorganica Acta. – 2005. – Vol. 2, No. 1. – P. 33-39 (in Ukraine).Abstract
By reaction of alkilation 3-aryloxychromones with epichlorohydrin were obtained 7-epoxyderivatives, which reacted with secondary amines to give the derivatives of 3-dialkylamino-2-hydroxypropane.
[18] Search for protein kinase CK2 inhibitors among 3-carboxy-4-aminoquinoline derivatives
V.M. Sapelkin, A.G. Golub, O.Ya. Yakovenko, V.G. Bdzhola, S.M. Yarmoluk
Ukrainica Bioorganica Acta. – 2005. – Vol. 2, No. 1. – Ñ. 28-32 (in Ukraine).Abstract
52 compounds from combinatorial library of 4-amino-3-carbethoxy-quinoline derivatives have been chosen using receptor-based virtual screening technology for studying their CK2 inhibition activity. It has been shown that 6 substances inhibit CK2 activity by more than 70 %. IC50 of these compounds ranged from 9 to 19 μM. The most potent inhibitor, 1.32 (3,6-dicarbethoxy-4-(4-acetamidophenylamino)quinoline, has IC50 9 μM. Model of binding of 4-amino-3-carbethoxy-quinoline derivatives to ATP-site of CK2 and structure-activity relationship are also proposed.
[17] Evaluation of 4H-4-chromenone derivatives as inhibitors of protein kinase CK2
À.O. Prykhod'ko, O.Ya. Yakovenko, A.G. Golub, V.G. Bdzhola and S.M. Yarmoluk
Biopolymers and Cell. – 2005. – V. 21, N 2. – P. 1-6.Abstract
Protein kinase CK2 (Casein Kinase 2) is ubiquitous serine/threonine protein kinase involved in various cell signal transduction pathways. Thus, CK2 is a new perspective target for anticancer drugs. The receptor-based virtual screening of 2000 compounds from combinatorial library of 4H-4-chromenones has been carried out in search for CK2-inhibitors. 90 compounds have been chosen for biological testing based on the score values calculated by DOCK 4.0 software. It has been revealed, that 3-(4-chloro-3,5-dimethylphenoxy)-7-(4-methoxyphenylcarbonyloxy)-4-oxo-4H-chromene (12) and 7-(4-fluorophenylcarbonyloxy)-4-oxo-3-(4-phenylphenoxy)-4H-chromene (14) inhibit CK2 activity with IC50 = 18.8 9 μM and IC50 = 22.4 9 μM, respectively.
[16] Inhibitors of protein kinase CK2
A. O. Prykhod'ko, G. G. Dubinina, S. M. Golovach, S. M. Yarmoluk
Ukrainica Bioorganica Acta. – 2004. – V. 1, 1–2. – P. 39–48 (in Ukraine).Abstract
This review presents general data on the CK2 inhibitors of various chemical structure. Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation. The CK2 negative role has also been proven in some mechanisms accompanying cell-controlled apoptosis (anti-apoptotic protecting function). Thus, the CK2 is considered as a perspective target for anticancer drugs. Our review presents the results of the search of CK2 inhibitors among known classes of the serinethreonine kinase antagonists: flavonoids, benzimidazole and benztriazole derivatives, aromatic sulfamides, fluoren and xantenone derivatives and others. The comparative analysis of CK2 inhibitors and their efficacy, specificity and probable mechanism of binding to active site has been done.
[15] Antiproliferative activities of some 7-hydroxy-3-aryloxy-2-trifluorometthyl-4H-4-chromenone derivatives against 60 human cancer cell lines
Prykhod’ko A.O., Dubinina G.G., Khilya V.P., Yarmoluk S.M.
Biopolymers and cell. – 2004. – V. 20, 1–2. – P. 159–163 (in Ukraine).Abstract
234 derivatives of 7-hydroxy-3-aryloxy-2-trifluorometthyl-4H-4-chromenones were synthesized and tested for antitumor activity in vitro against human cancer cell lines in NCI (National Cancer Institute, USA) bioassay. It was shown high cytostatic and cytotoxic activity for the tested compounds 1–8 (GI50 3.44–41.1 μM and LC50 from 49.6 μM). The relationship between structures of the tested compounds and their antiproliferative activities is discussed.
[14] Pat. 61626A (UA). Cl. C07D207/444, A61K31/40. The structures with antitumor activity among 1-benzyl-3-chloro-4-anilino-2,5-dihydro-1H-2,5-pyrroledione derivatives. 17.11.2003. Appl. 2003032383. 19.03.2003. 10 pp.
[13] Receptor-based design of protein kinase CK 2 inhibitors from the combinatorial library of 4H-4-chromenones
A. O. Prykhod'ko, G. G. Dubinina, O. Ya. Yakovenko., A. G. Golub., V. G. Bdzhola and S. M. Yarmoluk
Biopolymers and Cell. - 2004. - V.20, N 1. - P. (in English)Abstract
Protein kinase CK2 (Casein Kinase 2) is ubiquitous serine/threonine protein kinase involved in various cell signal transduction pathways. Thus, CK2 is a new perspective target for anticancer drugs.
We have carried out the computer receptor-based virtual screening of 2000 compounds from combinatorial library of 4H-4-chromenone (isoflavone) for design CK2-inhibitors. 90 Compounds have been chosen for biological testing based on the score values calculated by DOCK 4.0 software. It has been revealed, that 3-(4-chloro-3,5-dimethylphenoxy)-7-(4-methoxyphenylcarbonyloxy)-4-oxo-4H-chrome-ne (12) and 7-(4-fluorophenylcarbonyloxy)-4-oxo-3-(4-phenyl-phenoxy)-4H-chromene (14) inhibit CK2 activity with IC50 = 18,8 μM and IC50 = 22,4 μM, respectively.
[12] The relationship of antitumor activity with the structure of 3-chloro-4-(3-hydroxyanilino)-2,5-dihydropyrrole-2,5-diones
S. S. Tarnavsky, G. G. Dubinina, S. M. Golovach and S. M. Yarmoluk
Biopolymers and Cell. - 2003. - V.19, N 6. - P. 548-552 (in Ukrainian)Abstract
Fourteen derivatives of the 3-chloro-4-(3-hydroxyanilino)-2,5-dihydropyrrole-2,5-dione with various substitutents at 1 and 3 positions of maleimide cycle have been synthesized and tested for antitumor activity in vitro. Ten compounds selected after pre-screening and tested on 52 human tumor cell lines. It has been revealed that 1-(2,3-dichlorophenyl)-3-chloro-4-(3-hydroxyanilino)-2,5-dihydro-1H-2,5-pyrroledione and 1-benzyl-3-(3-hydroxyanilino)-4-phenylsulfanyl-2,5-dihydro-1H-2,5-pyrroledione suppress growth of some cancer cell lines with GI50 < 0.5 . 10-7 and 10-8 M.
[11] The search of antitumor activity among derivatives of the 2,5-dihydropyrrole-2,5-dione
S. S. Tarnavsky, G. G. Dubinina, S. M. Golovach and S. M. Yarmoluk
Biopolymers and Cell. - 2003. - V.19, N 3. - P. 287-291 (in Ukrainian)
Abstract
39 Derivatives of the 2,5-dihydropyrrole-2,5-dione were synthesized and tested on antitumor activity. The 1-benzyl-3-chloro-4-(3-hydroxyanilino)-2,5-dihydro-1H-2,5-pyrroledione (5.2) was selected after pre-screening and tested on 56 human tumor cell lines additionally. The compound 5.2 exhibits antitumor activity: GI50 2.68 mM, LC50 31.7 μM (cell line MDA-MB-435 (Breast Cancer)); GI50 3.35 μM, LC50 37.6 μM (cell line OVCAR-3 (Ovarian Cancer)); GI50 6.75 μM, 44.5 μM (cell line NCI-H23 (Non-small Cell Lung Cancer)).
[10] Antitumor activity of the 6-substituted derivatives of the 4-alkylaminoquinazolines
V. M. Sapelkin, I. E. Ìàkovenko, S. S. Lukashov, G.G. Dubinina and S. M. Yarmoluk
Biopolymers and Cell. - 2003. - V.19, N 5. - P. 467-472 (in Ukrainian)
Abstract
13 Derivatives of the 6-R-4-alkylaminoquinazoline were synthesized and tested on antitumor activity (in vitro). The synthesized compounds were tested on 56 human tumor cell lines. The four compounds (4.1, 4.9-4.11) inhibit proliferation of cancer cells in low micromolar concentrations. The 1-phenylethyl(4-quinazolinyl)amine (4.1) exhibit antitumor activity: GI50 2.29 mM; LC50 46.7 mM (cell line SK-MEL-5 (Melanoma)); the 6-bromo-4-quinazolinyl(tert-butyl)amine (4.10): GI50 3.82 mM; LC50 43.7 mM (cell line SK-MEL-5 (Melanoma)) and GI50 2.64 mM; LC50 44.2 (mM (cell line CAKI-1 (Renal Cancer)).
[9] Inhibitors of cyclin-dependent kinases. I. Synthesis of combinatorial libraries of 8-aminomethyl derivatives of 3-aryloxy-7-hydroxychromones and study of their antitumor activity
V. V. Arkhipov, A. O. Prykhod'ko, A. G. Golub, V. P. Khilya and S. M. Yarmoluk
Biopolymers and Cell. - 2003. - V.19, N 2. - P. 196-201 (in Ukrainian)
Abstract
Ñyclin-dependent kinases (CDK) play an important role in cell cycle regulation. CDK used as a targets in anticancer drug-discovery. These studies were aimed on the synthesis 3-aryloxy-7-hydroxy-8-aminomethylchromone derivatives, potential inhibitors of cyclin-dependent kinases. Biological anti-tumor testing of synthesyzed compounds was carried out in 60 human tumor cell lines.
[8] Interaction of 7-R-3-R1-7,8-dihydro-2Í,6Í-pyrrolo[3',4':4,5][1,3]thiazolo[3,2-b][1,2,4]triazine-2,6,8-triones with N-nucleophiles
G. G. Dubinina, S. M. Golovach, S. S. Tarnavsky and S. M. Yarmoluk
Ukr. Khim. Zh. - 2003. - V. 69, ¹ 4. - p. 35-39 (in Ukrainian).Abstract
Interaction of 7-R-3-R1-7,8-dihydro-2Í,6Í-pyrrolo[3',4':4,5][1,3]thiazolo[3,2-b][1,2,4]triazine-2,6,8-triones 1 with primary and secondary amines in acetic acid led to the opening of the 2,5-dihydropyrrole-2,5-dione's cycle and formation of 7-oxo-7H-[1,3]thiazolo[3,2-b][1,2,4]triazine-2,3-dicarboxamides 2. Interaction of (1) with hydrazine resulted in formation of the new heterocyclic system pyridazino[4',5':4,5][1,3]thiazolo[3,2-b][1,2,4]triazine-2,6,9-trione 3. The reaction of (1) with aqueous-ammonia solution produced [1,3]thiazolo[3,2-b][1,2,4]triazine-2-carboxamides 4 by aminolysis with destruction of maleimide ring and decarboxylation.
[7] Synthesis of potential biologically active substances on the base of 5-carboxymethylidene-2,4-thiazolidinedione
R.B. Lesyk, B.S. Zimenkovsky, S.M. Yarmoluk, I.Yu. Subtel’na
Pharmaceutical journal. – 2003. – ¹ 1. – P. 51–56 (in Ukraine).Abstract
Chemical methods for the synthesis of combinatorial libraries on the base of 5-substituted 2-arylamino-2-thiazoline-4-ones have been optimized. Prototropic tautomerism of 2-hydroxyanilino-2-thiazoline-4-ones and its 5-substituted analogues in solution was determined by the PMR-spectra. The lead-compound (5-(4-chlorophenylmethylidene)-2-(4-hydroxyanilino)-2-thiazoline-4-one) on the base of synthesized compounds prescreening has been selected for search of potential anticancer drugs with thiazolidine template.
[6] Interaction of 3,4-dichloromaleimides with N- and S-nucleophiles
G. G. Dubinina, S. S. Tarnavsky, S. M. Golovach and S. M. Yarmoluk
Ukr. Khim. Zh. - 2002. - V. 68, ¹ 8. - p. 47-51 (in Ukrainian).Abstract
The preparative method of the synthesis of 3,4-di(4-R1-phenylsulphanyl)-1-R-2,5-dihydro-1H-2,5-pyrrolediones II a-d was developed. The staggered nucleophilic substitution of the chlorine's atoms in 3,4-dichloromaleimides led to the formation of 1-R-3-(4-R1-phenylsulphanyl)-4-amino-2,5-dihydro-1H-2,5-pyrrolediones IV a-q. The interaction of 3,4-dichloro-N-H-maleimides with 1,3(S;N)-dinucleophiles - 6-R3-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-5-ones resulted in formation of condensed cyclic products - 3-R3-7,8-dihydro-2H,6H-pyrrolo[3',4':4,5][1,3]thiazolo[3,2-b][1,2,4]tri-azine-2,6,8-triones Va,b.
[5] Reaction of N-substituted 3,4-dichloromaleimides with a-mercaptoazaheterocycles
G. G. Dubinina, Yu. M. Volovenko, S. M. Yarmoluk, S. V. Shishkina, O. V. Shishkin
Heterocycles. - 2001. - N 11. - P. 2189-2198Abstract
Reaction of N-substituted 3,4-dichloromaleimides (1) with a-mercaptoazaheterocycles, 2-mercapto-1H-benzo[d]imidazole (2) and 6-alkyl-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-5-ones (4) in the presence of triethylamine, led to the formation of condensed thiazole ring resulting in 2,3-dihydro-1Í-benzo[4,5]imidazo[2,1-b]pyrrolo[3,4-d][1,3]thiazole-1,3-diones (5) and 7,8-dihydro-2Í,6Í-pyrrolo[3',4':4,5][1,3]-thiazolo[3,2-b][1,2,4]triazine-2,6,-8-triones (8), respectively. Refluxing of 8 in aqueous dioxane-triethylamine produced derivatives of 7-oxo-7Í-[1,3]thiazolo[3,2-b][1,2,4]triazine-2-carboxamides (9) by destruction of maleimide ring with decarboxylation. The structure of 9i was confirmed by X-Ray analysis. 1 reacted with 2-thioxo-1,2,3,4-tetrahydro-4-quinazolinone (3) with cyclization at N-1 and N-3 positions.
[4] The N4-aminoacid derivatives of 6-azacytidine: Syntheses and biological activity
I.V. Alekseeva, L.I. Palchikovska, A.S. Shalamay, S.S. Tarnavsky, L.N. Nosach,
N.S. Dyachenko
Biopolymers and Cell. - 1997. - V.13, N 4. - P. 285-290 (in Russian).
Abstract
Different methods of the synthesis of N4-derivatives of 6-azacytidine were investigated in conditions of simplified "silyl condensation" methods. Their antivirus activity with respect to the serotype 2 adenovirus in the culture of Hep-2 cells was studied. Primary specific activity of the compounds obtained was determined. Correlation between chemical structure of the new 6-azacytidine derivatives and their biological properties is discussed.
[3] The synthesis and spectroscopic investigations 3-thio-6-alkylamino derivaties 1.2.4-triazinone-5
S.S. Ognyanik, S.S. Tarnavsky, L.I. Sikora, I.V. Alekseeva
Ukr. Khim. Zhurn. - 1988. - N 11. - P.1197-1199 (in Russian).
Abstract
6-N-Aminoalkylated and 6-N-dialkylated derivatives of 1.2.4-triazine-3,5-dione and 3-thio-1.2.4-triazine-5-one were synthesized, and their UV- and VIS-spectra were studied.
[2] The glycosilation of 5-N-aminoacid derivatives of 6-azauracil and 2-thio-6-azauracil
S.S. Ognyanik, S.S. Tarnavsky, V.I. Kobylinska, I.V. Alekseeva, A.S. Shalamay
Ukr. Khim. Zhurn. - 1988. - N. 10. - P.1094-1098 (in Russian).
Abstract
5-N-Aminoacid derivatives of 6-azauracil and 2-thio-6-azauracil were synthesized by acetyltribenzoylribose glycosilation of trimethylsilyl ethers of 5-N-glycyl-, 5-N-alanyl- and their 2-thio- analogs in presence of SnCl4. The influence of solvent, concentration of catalyst, substituents in heterocycle on the yields of final products were studied.
[1] The synthesis of tritium-labelled 6-azauracil and 6-azacytidine
I.V. Alekseeva, G.V. Sidorov, A.S. Shalamay, S.S. Tarnavsky, A.F. Myasoedov, V.M. Koval, V.I. Kobylinska, V.P. Chernetsky
in: Methods of molecular Biology, Kyiv: Eds. Naukova Dumka, 1986, pp.52-58 (in Russian).
Abstract
The tritium-labelled 6-azauracil and 6-azacytidine were synthesized by glycosilation and next substitution of halogen of trimethylsillyl 5-bromo-6-azauracil derivative. 6-Azacytidine was synthesized by interection of 5-bromo-6-azauridine ribenzoate with P2S5 and substitution of sulfur to amino group (NH3/PrOH).
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