Department of Bioorganic Reaction Mechanisms

Head of Department - Andriy Vovk, Doctor of Science, Professor, Cor. Member NAS of Ukraine

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Лабораторія 3.1 Molecular mechanisms of regulation of cell metabolism 

Керівник лабораторії – д.б.н., проф. В.С.Кравець

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The Department of Bioorganic Reaction Mechanisms (until 2001 - the Department of Photosynthesis Chemistry) was established in 1963 on the basis of the biocatalyst group of the Department of Organic Reaction Mechanisms of the Institute of Organic Chemistry of the Academy of Sciences of Ukraine. Until 1999, the department was headed by Professor, Doctor of Chemical Sciences, Corr. Member NAS of Ukraine O.O. Yasnikov.

Recently, research in the department has focused on elucidating the mechanisms of model bioorganic transformations, synthesizing and studying the properties of new bioactive compounds in model systems, establishing the relationship between their structure and activity, and predicting the bioactivity of organic compounds by the molecularSAR method. The topics of his work are designing inhibitors of non-specific alkaline phosphatases, protein tyrosine phosphatases, acetylcholine cholinesterases, butyrylcholinesterases, lipoxygenases, glutathione-S-transferase, dihydrofolate reductase and other enzymes. The study of antioxidants and new spin probes continues.

Department staff (2017)

Mishchenko IM, Cand. chemical. Sciences
Tanchuk V.Yu., Cand. chemical. Sciences
Kobzar OL, Cand. chemical. of sciences
OV Musychka, Cand. chemical. of sciences
Kononets LA, Cand. biol. of sciences
Suhovyev OV, Cand. chemical. of sciences,
Melnik AK, engineer
Buldenko VM, PhD student
Ocheretnyuk AD engineer
Shulga YV engineer

Employees of the department (2016) - V.V. Trush, O.L. Kobzar, O.V. Sukhoveev, L.A. Kononets, A.I. Vovk, O.V. Musychka, V.Yu. Tanchuk, I.M. Mishchenko, A.D. Ocheretnyuk, V.M. Buldenko.

Department staff in the laboratory (2010) - A.I. Vovk, L.V. Babiy, N.V. Samus, I.M. Mishchenko, O.V. Musychka, L.A. Kononets, R.V. Bugas.

Defenses of dissertations in the Department (since 2000)

• Babiy L.V. Dissertation for the Candidate Degree in Chemical Sciences "Model Oxidative Transformations of Thiamine and Thiaminphosphates" - 2002
• O.V. Musychka Thesis for a Candidate Degree in Chemical Sciences “Kinetic dependences of inhibition of alkaline phosphatase from gut of L-cysteine by restored glutathione and phosphonic acids” - 2004.
• Bugas R.V. Thesis for a Candidate Degree in Chemical Sciences “Modeling of Transformations of Vitamin B1 and its Structural Thiazolium Analogues in Biological Transport Processes” - 2004.
• Kononets L.A. Thesis for a Candidate of Biological Sciences Degree - "Phosphonic Acids as Phosphatase Inhibitors" - 2012.
• Trush V.V. Thesis for a Candidate Degree in Chemical Sciences “Inhibition of Protein tyrosine phosphatase 1B by phosphonate derivatives of calix [4] arenas” - 2015.
• Kobzar O.L. Thesis for a Candidate Degree in Chemical Sciences “Potential Inhibitors of Protein tyrosine Phosphatases Based on Tetraazamacrocycles and Fullerenes” - 2015.
• Tanin V.A. Thesis for Candidate of Chemical Sciences Degree - “New Approaches to In silico Research on Protein tyrosine Phosphatase 1B Inhibitors” - 2016

Examples of the department's scientific developments (2012–2017)

1. Effective human protein tyrosine phosphatase inhibitors have been found on the platform of calixarenes, fullerenes and cyclic polyamines, which is important for the creation of new drugs for cancer, type 2 diabetes and other diseases.

2. The strategy of constructing non-purine xanthine oxidase inhibitors, which is a therapeutic target in the treatment of gout and hyperuricemia, among mono- and bis-carboxylated derivatives of aurons, is substantiated.

3. The inhibitory capacity of thiazolium salts as potential inhibitors of acetylcholinesterase and tyryl cholinesterase has been established, which creates the basis for further studies of thiazolium derivatives with the aim of finding a cure for Alzheimer's disease.

4. New spin probes and potential antioxidants based on 1-oxyl-2,2,6,6-tetramethylpiperidinyl-4-esters of adamantan- mono- and bis-carboxylic acids have been created.

5. New affinity adsorbents have been developed for the release of thiamine-binding proteins.

6. Among the synthesized 3-alkyloxycarbonylmethyl-4-methyl-5- (2-hydroxyethyl) thiazole salts, the compound 3-decyloxycarbonylmethyl-4-methyl-5- (2-hydroxyethyl) thiazolium chloride is promising for biomedical use.

7. Software for comparing and clustering the active surface of enzymes and proteins has been developed that can be used to select representative conformations of ligand binding centers in the computer simulation process.

8. A modified version of the well-known AutoDock 4.2 software package for molecular docking was created for the purpose of virtual screening of a large number of potential inhibitors. The modification includes a new search engine with a new algorithm that has been specifically designed to work with large size binding centers and mobile ligands, and includes new evaluation features and multithreading.

Selected publications

1. Muzychka O.V., Kobzar O.L., Popova A.V., Frasinyuk M.S., Vovk A.I. Carboxylated aurone derivatives as potent inhibitors of xanthine oxidase. Bioorg. Med. Chem. 2017, 25, 3606–3613.

2. Khilya O.V., Milokhov D.S., Kononets L.A., Kobzar O.L., Vovk A.I., Volovenko Yu.M.. Synthesis and evaluation of new 2,6-diamino-5-hetarylpyrimidines as inhibitors of dihydrofolate reductase. Monatsh. Chem. 2017, DOI 10.1007/s00706-017-2032-7.

3. Ocheretniuk A.D., Kobzar O.L., Mischenko I.M., Vovk A.I. N-Phenacylthiazolium alts as inhibitors of cholinesterases. French-Ukrainian J. Chem. 2017, 5, №2.

4. Burlaka Y.B., Sukhoveev O.V., Grin N.V., Khilchevskyi O.M., Verevka S.V. EPR spectroscopy studies of changes in erythrocyte membranes in patients with laryngeal cancer. Experimental Oncology 2017, 39, 49–52.

5. Tanchuk V.Yu., Tanin V.O. Vovk A.I., Poda G. A New, Improved Hybrid Scoring Function for Molecular Docking and Scoring Based on AutoDock and AutoDock Vina. Chem. Biol. Drug Des. 2016, 87, 618-625.

6. Melnyk, A. K., Sukhoveev, O. V., Kononets, L. A., Khilchevsky, O. M., Shulga, S. M., Kukhar, V. P., & Vovk, A. I. An EPR spin probe study of liposomes from sunflower and soybean phospholipids. J. Liposome Res. 2016, 26, 80-86.

7. Trush V.V., Kharchenko S.G., Tanchuk V.Yu., Kalchenko V.I., Vovk A.I. Phosphonate monoesters on a thiacalix[4]arene framework as potential inhibitors of protein tyrosine phosphatase 1B. Org. Biomol. Chem. 2015, 13, 8803-8806.

8. Trush V.V., Tanchuk V.Y., Cherenok S. O., Kalchenko V.I., Vovk A.I.. Evaluation of inhibition of protein tyrosine phosphatase 1B by calixarene-based ?-ketophosphonic acids. Chem. Biol. Lett. 2015, 2, 1-5.

9. Kobzar O.L., Shevchuk M.V., Lyashenko A.N., Tanchuk V.Yu., Romanenko V.D., Kobelev S.M., Averin A.D., Beletskaya I.P., Vovk A.I., Kukhar V.P. Phosphonate derivatives of tetraazamacrocycles as new inhibitors of protein tyrosine phosphatases. Org. Biomol. Chem. 2015, 13, 7437-7444.

10. Kobzar O.L., Trush V.V., Tanchuk V.Yu., Vovk A.I. Inhibitory potential of polyhydroxylated fullerenes against protein tyrosine phosphatase 1B. Ukr. Biochem. J. 2015, 87, 24-31.

11. Kobzar O.L. , Trush V.V. , Tanchuk V.Yu. , Voronov I.I. , Peregudov A.S. , Troshin P.A. , Vovk A.I. Polycarboxylic fullerene derivatives as protein tyrosine phosphatase inhibitors . Mendeleev Commun. 2015, 25, 199-201.

12. Tanchuk V., Tanin V., Vovk A., Poda G. A new scoring function for molecular docking based on AutoDock and AutoDock Vina . Curr. Drug Discov. Technol. 2015, 12, 170-178.

13. Mkrtchyan G., Aleshin V., Parkhomenko Y., Kaehne T., Di Salvo M. L., Parroni A., Contestabile R., Vovk A., Bettendorff L., Bunik V. Molecular mechanisms of the noncoenzyme action of thiamin in brain: biochemical, structural and pathway analysis Scientific Reports 2015, 5, Article number: 12583, doi:10.1038/srep12583.

14. Kobzar O.L., Trush V.V., Tanchuk V.Yu., Zhilenkov A.V., Troshin P.A., Vovk A.I. Fullerene derivatives as a new class of inhibitors of protein tyrosine phosphatases. Bioorg. Med. Chem. Lett. 2014, 24, 3175–3179.

15. Trush V.V., Tanchuk V.Y., Cherenok S.O., Kalchenko V.I., Vovk A.I. Calix[4]arene alpha-hydroxymethylphosphonic acids as potential inhibitors of protein tyrosine phosphatases. Org. Pharm. Chem. 2014, 1, 39-42.

16. Komisarenko S.V., Kosterin S.O., Lugovskoy E.V., Cherenok S.O., Tanchuk V.Yu., Vovk A.I., Kalchenko V.I. Сalixarene methylene bisphosphonic acids as effectors of biochemical processes. In Book: “Ligands: synthesis, characterization and role im biotechnology”. Nova Science Publishers Inc. N.-Y., 2013. 304 p. pp. 67-116.

17. Tanchuk V.Yu., Tanin V.O., Vovk A.I.. Analysis of сonformational flexibility of loop 110-120 of protein tyrosine phosphatase 1B. Ukr. Biochim. J., 2013, 85, 73-80.

18. Kalchenko V. I., Cherenok S.O., Kosterin S.O., Lugovskoy E.V., Komisarenko S.V., Vovk A.I., Tanchuk V.Y., Kononets L.A., Kukhar V.P. Calixarene phosphonous acids: synthesis and biological activity. Phosphorus, Sulfur, and Silicon 2013, 188, 232-237.

19. Tanchuk V.Yu., Tanin V.O., Vovk A.I. QSAR models for predicting protein tyrosine phosphatase 1B inhibition by structurally diverse inhibitors. Org. Pharm. Chem. 2013, 11, 51-56.

20. Trush V.V., Cherenok S.O., Tanchuk V.Yu., Kukhar V.P., Kalchenko V.I., Vovk A.I. Calix[4]arene methylenebisphosphonic acids as inhibitors of protein tyrosine phosphatase 1B Bioorg. Med. Chem. Lett. 2013, 23, 5619–5623.

21. Khakina E.A., Yurkova A.A., Peregudov A.A., Troyanov S.I., Trush V.V., Vovk A.I., Mumyatov A.V., Martynenko V.M., Balzarini J. , Troshin P.A. Highly selective reactions of C60Cl6 with thiols for synthesis of functionalized [60]fullerene derivatives. Chem. Commun. 2012, 48, 7158-7160.

22. Tanchuk V.Y., Tanin V.O., Vovk A.I. Classification of binding site conformations of protein tyrosine phosphatase 1B. Chem Biol Drug Des. 2012, 80, 121-128.

23. Cherenok S.O., Yushchenko O.A., Tanchuk V.Yu., Mischenko I.M., Samus N.V., Ruban O.V., Matvieiev Y.I., Karpenko J.A., Kukhar V.P., Vovk A.I., Kalchenko V.I. Calix[4]arene-?-hydroxyphosphonic acids. Synthesis, stereochemistry, and inhibition of glutathione S-transferase. ARKIVOC 2012, 278 – 298.

24. Vovk A.I., Mischenko I.M., Cherenok S.O., Tanchuk V.Yu., Kalchenko V.I., Kukhar V.P. Phosphorylated calix[4]arenes as inhibitors of glutathione S-transferase. Phosphorus, Sulfur, and Silicon 2011, 186, 961-963.
25. Vovk A.I., Tanchuk V.Yu., Kononets L.A., Cherenok S.O., Drapailo A.B., Kalchenko V.I., Kukhar V.P. A novel approach to the design of phosphonate inhibitors of protein tyrosine phosphatase. Phosphorus, Sulfur, and Silicon 2011, 186, 958-960.

26. Kachkovskyi G.O., Kononets L.A., Tanchuk V.Yu., Vovk A.I., Kolodiazhnyi O.I. Synthesis and Evaluation of 1-Aryl-1-(7-carboxyisoindolin-1-one-2-yl)methyl-phosphonic Acid Derivatives as Inhibitors of Protein Tyrosine Phosphatase. Phosphorus, Sulfur, and Silicon 2011, 186, 956-957.

27. Shapoval G.S., Babii L.V., Kruglyak O.S., Vovk A.I. Antioxidant activity of thiamine and its structural analogs in reactions with electrochemically generated hydroxyl radicals and hydrogen peroxide. Theor. Exp. Chem. 2011, 47, 55-60.

28. Vovk A.I., Kononets L.A., Tanchuk V.Yu., Cherenok S.O., Drapailo A.B., Kalchenko V.I., Kukhar V.P. Inhibition of Yersinia protein tyrosine phosphatase by phosphonate derivatives of calixarenes. Bioorg. Med. Chem. Lett. 2010, 20, 483-487.

29. Vovk A.I., Kononets L.A., Tanchuk V.Yu., Drapailo A.B., Kalchenko V.I., Kukhar V.P. Thiacalix[4]arene as Molecular Platform for Design of Alkaline Phosphatase Inhibitors. J. Incl. Phenom. Macrocycl. Chem. 2010, 66, 271-277.

30. Vovk A.I., Shivanyuk A.M., Bugas, R.V., Muzychka, O.V., Melnyk, A.K. Antioxidant and antiradical activities of resorcinarene tetranitroxides. Bioorg. Med. Chem. Lett. 2009, 19, 1314-1317.

31. Vovk A.I., Mischenko I.M., Tanchuk V.Yu., Kachkovskii G.A., Sheiko S.Yu., Kolodyazhnyi O.I., Kukhar V.P. Stereoselectivity of binding of (N-benzylamino)benzylphosphonic acids to prostatic acid phosphatase. Bioorg. Med. Chem. Lett. 2008, 18, 4620–4623.

32. Vovk A.I., Chuiko A.L., Kononets L.A., Tanchuk V.Yu., Muravyova I.V., Lozynsky M.O., Kukhar V.P. Inhibition of alkaline phosphatase by thioureido derivatives of methylenebisphosphonic acid. Russ. J. Bioorg. Chem. 2008, 34, 60-66.

33. Vovk A., Kalchenko V., Tanchuk V., Muzychka O., Muravyova I., Shivanyuk A., Cherenok S., Kukhar V. Сalixarene methylenebisphosphonic acids: alkaline phosphatase inhibition and docking studies. Phosphorus, Sulfur, and Silicon 2008, 183, 625-626.

34. Garazd M.M., Muzychka O.V., Vovk A.I., Nagorichna I.V., Ogorodniichuk A.S. Modified coumarins. 27. Synthesis and antioxidant activity of 3-substituted 5,7-dihydroxy-4-methylcoumarins. Chem. Nat. Comp. 2007, 43, 19-23.

35. Kochubey S.M., Vovk A.I., Bondarenko O.Yu., Shevchenko V.V., Bugas R.V., Melnyk A. K., Tanchuk V.Yu. Heterogeneity of thylakoid membranes studied by EPR spin probe. Biochemistry (Moscow) 2007, 72, 558-564.

36. Cherenok S., Vovk A., Muravyova I., Shivanyuk A., Kukhar V., Lipkowski J., Kalchenko V. Calix[4]arene ?-aminophosphonic acids: asymmetric synthesis and enantioselective inhibition of an alkaline phosphatase. Org. Lett. 2006, 8, 549-552.

37. Vovk A.I., Kharhenko O.V., Kharitonenko A.I., Kukhar V.P., Babiy L.V., Kazachkov M.G., Melnyk A.K., Khichevsky О.M. Hydrophobic nitroxyl radicals inhibit linoleyl alcohol oxidation by 5-lipoxygenase. Russ. J. Bioorg. Chem. 2004, 30, 391-395.

38. Vovk A.I., Kalchenko V.I., Cherenok S.A., Kukhar V.P., Muzychka O.V., Lozynsky M.O. Calix[4]arene methylenebisphosphonic acids as calf intestine alkaline phosphatase inhibitors. Org. Biomol. Chem. 2004, 2, 3162-3166.

In the cafe. On the left - V.M. Buldenko, O.L. Kobzar, A.I. Vovk. Right - A.D. Ocheretnyuk, O.V. Muzychka, I.M. Mishchenko, L.A. Kononets.

O.L. Kobzar (foreground), A.D. Ocheretnyuk and V.M. Buldenko.

The research is carried out by the graduate student A.O. Ocheretnyuk.

Graduate student V.M. Buldenko at work.

V.Yu. Tanchuk (right) and V.V. Tanin (photo 2016)

Yu.V. Shulga is the youngest employee of the department (2017).

Contact Information

02660, Київ-94, вул Академіка Кухаря, 1, Україна
Тел.: +38 (044) 2732553
Факс.: +38 (044) 5732552
e-mail: vovk@bpci.kiev.ua