Institute of Bioorganic Chemistry and Petrochemistry National Academy of Science of Ukraine

Department 2
Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases

Contacts

Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases
V.P.Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine.

Volodymyr S. Brovarets
Doctor of Chemical Sciences, Professor


Address and other contact information:
1, Murmanskaya Str., Kiev, 02660, Ukraine.
Tel.: +38 (044) 2967154
Fax.: +38 (044) 5732561
e-mail: brovarets@bpci.kiev.ua

A General Direction of Scientific Investigations:
The elaboration of synthetic approaches to new functionalized derivatives of
azoles and azines on the basis of original reagents with N-, P-, S-containing groups.in the last 20 years more than founded on the basis of available amidoalkylating substances 100 original reagents have been introduces into practice of fine organic synthesis. They proved to be very suitable for preparation of new derivatives of various nitrogen heterocycles, among which the substances with high insecticidal, bactericidal and fungicidal activity as well as analgetic, neurotropic and antitumor preparates were found.
It should be mentioned first of all the use of enamides for preparations of 4- and 5-functionalized oxazoles.
It was shown the importance of the new vinylphosphonium reagents as synthetic tools in chemistry of five- and six-membered nitrogen heterocycles. It is quite evident that a variety of cyclization products prepared on the basis of these reagents, may be widely used for studying transmission of electron effects in heterocyclic systems, region- and stereochemical peculiarities of some processes with participation of the reagents as well as for elucidation of a relationship between structure and physiological activity of many new types of heterocyclic compounds.
It is worth mentioning that on original plant grows regulator Metiur one from a functionalized pyrimidine base was developed in our Department. The study of close analogues of Metiur seems to be promising and can be conducted together with a special biological laboratory.
Screening of low molecular weight five and six-membered heterocyclic compounds as new effective stimulators of plant growth and development.

Scientific Interests of the Department:

Organic chemistry, chemistry of heterocyclic compounds, bioorganic chemistry, fine chemicals, agriculture, plant biotechnology.


Research Groups of the Department:

Group of synthesis and study of phosphoruscontaining heterocyclic compounds properties
Head of group Oleksandr Golovchenko, Ph.D, Senior researcher

Group of Synthesis and Study of Flavonoids properties
Head of group Frasinyuk Mikhailo Sergiyovich, Ph.D. Senior researcher

Group of Biological Screening
Head of group Tsygankova Victoria Anatolyivna, Sci. D. in Biotechnology, Principal researcher, Senior Staff Scientist

Group of synthesis and study of pyrazolotriazinones properties
Head of group Shablykin Oleh Valentinovich, Ph.D. Senior Researcher


Our scientific directions

New Approaches to Synthesis of Substituted Azoles

Screening of low molecular weight five- and six-membered heterocyclic compounds bioregulative activity

Proposals:

a) We propose to make a contract with a Company or Institute of Biological or Medicinal trend for testing several hundreds of new heterocyclic compounds per year with structure reliable established.
b) The Department can execute any specific project proposed by anyone Company or Institute that it will be concerned with heterocyclic compounds.
c) It is assumed that the total numbers of participants involved in this project will be more than 15 highly skilled researchers capable of solving complex problems of bioorganic chemistry.
d) The realization of this project will be ensured not only by scientific ideas but also by modern technical facility (reliable elemental analisis, high performance liquid chromatography, IR, UV, high-resolution NMR-spectroscopy, X-


Examples of Scientific Developments of the Department


Heterocyclizations based on chlorocontaining enamides

The enamides are useful reagents for the synthesis of a large number of mono- and polycyclic azaheterocycles


Synthesis of new phosphonopeptidomimetics based on 4-phosphorilated derivatives of 1,3-oxazoles

Developed preparative methods of synthesis of new aminophosphonic acids, phosphorilated peptides and phosphonopeptidomimetics - potential bioregulators


SCIENTIFIC PROJECTS OF THE DEPARTMENT

The department's research is aimed at the development of preparative syntheses of potential bioregulators of heterocyclic nature on the basis of original reagents created by the department's staff. This approach makes it possible to synthesize specific derivatives of azaheterocycles that are difficult or impossible to synthesize in other ways, especially with respect to the regio-selective introduction of nitrogen, sulfur and phosphorus-containing pharmacophoric residues and transport groups into certain positions of the heterocyclic fragment. The search for bioactive drugs among the synthesized azaheterocycles is carried out by the staff of other departments of the biological direction of our Institute and experts of the Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, the Institute of Botany of the National Academy of Sciences of Ukraine, the Zaporizhzhya Medical University and the University of Kentucky (USA), the National Institute of Health (USA) , National Cancer Research Institute (USA).

Development of methods of synthesis of new nitrogen-containing heterocyclic compounds

Substituted azoles

Derivatives of 1,3-oxazole

On the basis of methyl esters of 2-acylamino-3,3-dichloroacrylic acids, a number of biologically active functionally substituted oxazoles were synthesized


A number of other oxazoles were synthesized using unique polycentric reagents - N-(2,2-dichloro-1-cyanovinyl) amides


Further transformation of unsaturated chloroform azlactones made it possible to synthesize a number of other heterocyclic compounds


Derivatives of 1,3-oxazole(thiazole)sulphonylchlorides

N-Substituted amides were introduced into various cyclic condensations to obtain chlorosulfonyl derivatives of oxazole and thiazole and corresponding sulfonamide derivatives as potential broad-spectrum action bioregulators. Among these compounds, drugs with extremely high antitumor and antiviral activity have been detected.


STUDY OF BIOLOGICAL ACTIVITY OF NITROGEN-CONTAINING HETEROCYCLES

Screening of low molecular weight five- and six-membered heterocyclic compounds
as new effective growth and plant growth promoters


PUBLICATIONS:

  • V. M. Sviripa, A. A. Gakh, V. S. Brovarets, A. V. Gutov, B. S. Drach. Original Approach to New Derivatives of [1,3]Oxazolo[4,5-d]pyrimidine // Synthesis. 2006. Vol. 20. p. 3462-3466.
  • Balia A.G., Belyuga A.G., Brovarets V,S., Vasylenko A.N., Turov A.V., Gakh A.A., Drach B.S. Original recyclization of s-phenacyl derivatives of 4-acylamino-2-mercapto-1,3-oxazoles and their analogues // Heteroatom Chem. - 2007. - Vol. 18, No. 4, - P. 432-437.
  • Shablykin O.V., Brovarets V.S., Rusanov E.B., Drach B.S. Peculiar reaction of N-2-acyl derivatives of 2-aryl-5-hydrazino-1,3-oxazole-4-carbonitriles with the Lawesson reagent // Heteroatom Chem. - 2007. - Vol. 18, No. 7. - P. 782-785.
  • V. M. Prokopenko, V. N. Sviripa, V. S. Brovarets, E. B. Rusanov, B. S. Drach. Successive reaction of 2-aryl-4-dichloromethylideneoxazol-54H-ones with 2-amino-1,3-thiazoles and strongly basic nitrogen-containing reagents // Russ. J. Gen. Chem. 2008. Vol. 78(4). p. 649-654.
  • Shablykin O.V., Gakh A.A., Brovarets V.S., Rusanov E.B., Drach B.S. A facile synthesis of new 1,2-dihydro-2,5-[1,3,2]diazaphosphinine derivatives starting from 2-benzoylamino-3,3-dichloroacrylonitrile // Heteroatom Chem. - 2008. - Vol. 19, No. 5. - P. 506-511.
  • Demydchuk B.A., Brovarets V.S., Vasilenko A.N., Drach B.S. Preparative conversion of chloralamides to 2,5-diaryl-3a,6a-dihydro[1,3]thiazolo[4,5-d][1,3]thiazoles with the Lawesson reagent // Heteroatom Chem. - 2008. - Vol. 19, No. 7. - P. 677-681.
  • Syntheses of fluorinated 1,3-oxazoles, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and oxazolo[4,5-d]pyrimidines. V.S. Brovarets, O.P. Mityukhin, A.V. Golovchenko, B.S. Drach. 232nd American Chemical Society National Meeting. Exposition, San Francisco, CA, from 9 to 15 September 2006. Division of Fluorine Chemistry. . . "Fluorinated Heterocycles" / Eds. A.A. Gakh, K.L. Kirk. Washington, American Chemical Society, 2009, P. 281-289.
  • I. Subtel'na, D. Atamanyuk, E. Szymanska, K. Kiek-Kononowicz, B. Zimenkovsky, O. Vasylenko, A. Gzella, R. Lesyk. Synthesis of 5-arylidene-2-amino-4-azolones and evalnations of their anticancer activity. Bioorganic& Medicinal Chemistry. 2010. N 18. P. 5090-5102.
  • V. M. Prokopenko, S. G. Pil'o, V. S. Brovarets, A. N. Vasilenko, B. S. Drach. Reaction of 2-aryl-4-dichloromethylidene-1,3-oxazol-5(4H)-ones with 2-aminopyridine // Russ. J. Gen. Chem. 2010. Vol. 80(1). p. 121-126.
  • V. M. Prokopenko , S. G. Pil'o, V. S. Brovarets. Synthesis of 4-hetaryl-substituted 5-amino- and 5-sulfanyl-1,3-oxazole derivatives // Russ. J. Gen. Chem. 2011. Vol. 81(2). p. 405-410.
  • Isorhodanine and Thiorhodanine Motifs in the Synthesis of Fused Thiopyrano[2,3-d]-
    [1,3]thiazoles. D. Kaminskyy, O. Vasylenko, D. Atamanyuk, A. Gzella, R. Lesyk. SYNLETT. 2011. N 10. P. 1385-1388.
  • S. A. Chumachenko, O. V. Shablykin, A. N. Vasilenko, V. S. Brovarets. Synthesis and some properties of 5-alkylamino-2-(phthalimidoalkyl)-1,3-oxazole-4-carbonitriles // Chemistry of Heterocyclic Compounds. 2011. Vol. 47(8). p. 1020-1028.
  • B.A. Demydchuk, K.M. Kondratyuk, A.N. Kornienko, V.S. Brovarets, R.Ya. Vasylyshyn, A.A. Tolmachev, O. Lukin. A Facile Synthesis of 1,3-thiazole-4-sulfonyl chlorides. Syntetic Commun. 2012. Vol.42. P. 2866-2875.
  • A.N. Kornienko, S. G. Pil'o, V. M. Prokopenko, V. S. Brovarets. Synthesis of 2-aryl-4-cyano-1,3-oxazole-5-sulfonyl chlorides and N-substituted sulfonamides // Russ. J. Gen. Chem. 2012. Vol. 82(11). p. 1855-1858.
  • A Novel Synthetic Approach to Phosphorylated Peptidomimetics. O.I. Lukashuk, K.M. Kondratyuk, A.V. Golovchenko, V.S. Brovarets, V.P. Kukhar. Heteroatom Chem. 2013. Vol.24. 4. P. 289-297.
  • Synthesis of 5-amino-2-aminoalkyl-1,3-oxazol-4-ylphosphonic acid derivatives and their use in the preparation of phosphorylated peptidomimetics. K.M. Kondratyuk, O.I. Lukashuk, A.V. Golovchenko, I.V. Komard, V.S. Brovarets, V.P. Kukhar. Tetrahedron. 2013. Vol.69. P. 6251-6261.
  • A.N. Kornienko, S. G. Pil'o, V. M. Prokopenko, V. S. Brovarets. Amidophenacylating reagents in synthesis of new derivatives of 1,3-oxazole- and 1,3-thiazole-4-sulfonyl chlorides and corresponding sulfonamides // Russ. J. Gen. Chem. 2014. Vol. 84(4). p. 686-692.
  • A.N. Kornienko, S. G. Pil'o, V. M. Prokopenko, V. S. Brovarets. Synthesis and properties of 2-substituted 5-chloro-1,3-oxazole-4-carboxamides // Russ. J. Gen. Chem. 2014. Vol. 84(6). p. 1186-1189.
  • S. A. Chumachenko, O. V. Shablykin, V. S. Brovarets. Interaction of 5-(Morpholin-4-Yl)-2-(4-Phthal-Imidobutyl)- and 5-(Morpholin-4-Yl)-2-(5-Phthal-Imidopentyl)-1,3-Oxazole-4-Carbonitriles with Hydrazine Hydrate // Chemistry of Heterocyclic Compounds. 2015. Vol. 50(12). p. 1727-1730.
  • Victoria Tsygankova, Elena Shysha, Yaroslav Andrusevich, Anatoly Galkin, Galina Iutynska, Alla Yemets, Yaroslav Blume. Using of new microbial biostimulants for obtaining in vitro new lines of Triticum aestivum L. cells resistant to nematode H. avenae / Tsygankova V.A., Shysha E.N., Andrusevich Ya.V., Galkin A.P., Iutynska G.A., Yemets A.I., Blume Ya.B. // European Journal of Biotechnology and Bioscience. - 2016. - V.4, Issue 4. - P. 41-53. (RJIF (Research Journal Impact Factor): 5.22). ICV (Index Copernicus Value) 2015: 72.59. http://www.biosciencejournals.com/archives/2016/vol4issue4/4-4-26.1.pdf
  • Tsygankova V.A., Bayer O.O., Andrusevich Ya.V., Galkin A.P., Brovarets V.S., Yemets A.I., Blume Ya. B. Screening of five and six-membered nitrogen-containing heterocyclic compounds as new effective stimulants of Linum usitatissimum L.organogenesis in vitro / Tsygankova V.A., Bayer O.A., Andrusevich Ya.V., Galkin A.P., Brovarets V. S., Yemets A.I., Blume Ya.B. // Int. J. Med. Biotechnol. Genetics. - 2016. - S2:001. - P. 1-9. http://scidoc.org/specialissues/IJMBG/S2/IJMBG-2379-1020-S2-001.pdf.
  • Victoria Tsygankova, Yaroslav Andrusevich, Olexandra Shtompel, Artem Hurenko, Roman Solomyannyj, Galyna Mrug, Mikhaylo Frasinyuk, Volodymyr Brovarets. Stimulating effect of five and six-membered heterocyclic compounds on seed germination and vegetative growth of maize (Zea mays L.). International Journal of Biology Research. 2016. V.1 Issue 4, P. 1-14. (RJIF (Research Journal Impact Factor): 5.22).http://www.biologyjournal.in/archives/2016/vol1/issue4/1-4-16
  • Victoria Tsygankova, Yaroslav Andrusevich, Olexandra Shtompel, Artem Hurenko, Roman Solomyannyj, Galyna Mrug, Mikhaylo Frasinyuk, Volodymyr Brovarets. Stimulating effect of five and six-membered heterocyclic compounds on seed germination and vegetative growth of maize (Zea mays L.). International Journal of Biology Research. 2016. V.1 Issue 4, P. 1-14. (RJIF (Research Journal Impact Factor): 5.22). http://www.biologyjournal.in/archives/2016/vol1/issue4/1-4-16
  • Victoria Tsygankova, Yaroslav Andrusevich, Olexandra Shtompel, Stepan Pilyo, Volodymyr Prokopenko, Andrii Kornienko, Volodymyr Brovarets. STUDY OF GROWTH REGULATING ACTIVITY DERIVATIVES OF [1,3]OXAZOLO[5,4-d]PYRIMIDINE AND N-SULFONYL SUBSTITUTED OF 1,3-OXAZOLES ON SOYBEAN, WHEAT, FLAX AND PUMPKIN PLANTS. International Journal of Chemical Studies. 2016. V. 4, Issue 5. P. 106-120. (GIF (Global Impact and Quality Factor): 0.565, RJIF (Research Journal Impact Factor): 4.86), NAAS Rating (National Academy of Agricultural Sciences): 5.31, ICV (Index Copernicus Value) 2015: 70.91. http://www.chemijournal.com/archives/?year=2016&vol=4&issue=5&part=B&ArticleId=325
  • Victoria Tsygankova, Yaroslav Andrusevich, Olexandra Shtompel, Olexandr Myroljubov, Artem Hurenko, Roman Solomyanny, Galyna Mrug, Mykhaylo Frasinyuk, Oleg Shablykin, Volodymyr Brovarets. Study of Auxin, Cytokinin and Gibberellin-like Activity of Heterocyclic Compounds Derivatives of Pyrimidine, Pyridine, Pyrazole and Isoflavones. European Journal of Biotechnology and Bioscience. 2016. V. 4, Issue 12. P. 29-44. (RJIF (Research Journal Impact Factor): 5.22), ICV (Index Copernicus Value) 2015: 72.59. http://www.biosciencejournals.com/archives/2016/vol4/issue12/4-11-21
  • Victoria Tsygankova, Yaroslav Andrusevich, Olexandra Shtompel, Olexandr Romaniuk, Marharyta Yaikova, Artem Hurenko, Roman Solomyanny, Esma Abdurakhmanova, Svitlana Klyuchko, Oleksandr Holovchenko, Olga Bondarenko, Volodymyr Brovarets. Application of Synthetic Low Molecular Weight Heterocyclic Compounds Derivatives of Pyrimidine, Pyrazole and Oxazole in Agricultural Biotechnology as a New Plant Growth Regulating Substances. Int J Med Biotechnol Genetics. 2017; S2:002, 10-32. http://scidoc.org/specialissues/IJMBG/S2/IJMBG-2379-1020-S2-002.pdf
  • Victoria Tsygankova, Elena Shysha, Anatoly Galkin, Lyudmila Biliavska, Galina Iutynska, Alla Yemets, Yaroslav Blume. Impact of Microbial Biostimulants on Induction of Callusogenesis and Organogenesis in the Isolated Tissue Culture of Wheat in vitro. J. Med. Plants. Stud. 2017. Volume 5, Issue 3. P. 155-164. (RJIF (Research Journal Impact Factor): 5.69), NAAS Rating (National Academy of Agricultural Sciences): 3.53, ICV (Index Copernicus Value) 2015: 70.52).
    http://www.plantsjournal.com/archives/2017/vol5issue3/PartC/5-3-6-139.pdf

  • Kovalishyn V., Brovarets V., Dlagodatnyi V., Kopernyk I., Hodyna D., Chumachenko S., Shablykin O., Kozachenko O., Vovk M., Barus M., Bratenko M., Metelytsia L. QSAR studies, synthesis and antibacterial assessment of new inhibitors against multidrug-resistant Mycobacterium tuberculosis.Current Drug Discovery Technologies, 2017. -Vol.14, 1. - P.25-38.
  • Demydchuk B.A., Rusanov E.B., Rusanova S.A., Brovarets V.S. Regioselective synthesis of bicyclic by 1,3,5-triazepine system starting from tetrachloro-2-aza-1,3-butadienes.Current Chemistry Letters, 2017. - 6. - P.49-54.
  • Holovchenko O., Naumenko A., Vydzhak R., Abdurakhmanova E., Prostota Ya., Kachkovsky O., Brovarets V. Electronik and spectral properties of phosphonium ylides-betaines, derivatives of 2-oxazoline-5-one.Eur. Chem. Bull., 2017 - V.6, N9. - 380-392.
  • M.V.Kachaeva, D.M.Hodyna, I.V.Semenyuta, S.G.Pilyo, V.M.Prokopenko, V.V.Kovalishyn, L.O.Metelytsia, V.S.Brovarets Design, synthesis and evaluation of novel sulfonamides as potential anticancer agents.Computational biology and chemistry, 2018.-V.74.-P.294-303.
  • Solomyannyi Roman, Slivchuk Sergii, Smee Donald, Choi Jung-ae, Rusanov Eduard, Zhirnov Victor, Brovarets Volodymyr.In vitro activity of the novel pyrimidines and their condensed derivatives against poliovirus.Current Bioactive Comp., 2018. - V.14, N14. - P.1-9.
  • Kachkovsky Alexey, Obernikhina Nataliya, Prostota Yaroslav, Naumenko Antonina, Melnyk Dmitro, Yashchuk Valeriy.Estimation of the basicity of the donor strength of terminal groups in cationic polymethine dyes.J.Molec.Structure, 2018. - V.1154. - P. 606-618.
  • Ocheretniuk A.D., Kobzar O.L., Kozachenko O.P., Brovarets V.S., Vovk A.I..Synthesis and the activity assessment of adamantylcontaining thiazolium inhibitors of butyrylcholinesterase.J.Org.Pharm., 2017. - V.15, N4(60). - P.48-55.
  • Nizhenkovska I., Romanenko A., Sedko K., Grusha M., Brovarets V., Golovchenko A..Studying of vazoactive properties of diethyl esther of 5-alkylamine-2-{N-[N-benzoyl-(4-methylbenzal)-glycyl]aminomethyl}-1,3-oxazole-4-ylphosphonic acid on rat,s isolated aorta .Pharmacology and Drug Toxicology, 2015. - 6(46). - P.76-83.
  • Chalyk B.A., Hrebeniuk K.V., Gavrilenko K.S., Shablykin O.V., Yanshyna O.O., Bash D., Mykhailik P.K., Liashuk O.S., Grygorenko O.O. Synthesis of Bi- and Polyfunctional Isoxazoles from Amino Acid-Derived Halogenoximes and Active Methylene Nitriles.Eur.J.Org.Chem., 2018. - V.22. - P.2753-2761.
  • Popova A.V., Bondarenko C.P., Frasinyuk M.S., Wen Zhang, Xie Yanji, Martin Zachary M., Cai Xianfeng, Fiandalo Michael V., Mohler James L., Liu Chunming, Watt David S., Sviripa V.M..Efficient synthesis of aurone Mannich bases and evaluation of their antineoplastic activity in PC-3 prostate cancer cells.Chemical Papers, 2018. - V.72,N10. - P.2443-2456.
  • Velihina Ye., Kachaeva M.V., Pilyo S.G., Zhirnov V.V., Brovarets V.S. Synthesis, Characterization, and Vitro Anticancer Evaluation of 7-Piperazin-substituted [1,3]oxazolo[4,5-d]pyrimidines.Der Pharma Chemica, 2018. - V.10,N9. - 1-10.
  • Mrug G.P., Demydchuk B.A., Bondarenko S.P., Sviripa V. M., Wyrebek P., Mohler J. L., Fiandalo M.V., Liu C., Frasinyuk M.S., Watt D.S..A Direct Synthesis of 2-(?-Carboxyalkyl)-isoflavones from ortho-Hydroxylated Deoxybenzoins.Eur. J. Org. Chem., 2018. - V. 39. - P.5460- 5463.
  • Tsygankova, V.A., Andrusevich, Y. V., Galkin, A. P., Biliavska, L. O., Galagan, T. O., Yemets, A. I., et al. (2019). RNAi-mediated resistance against plant parasitic nematodes of wheat plants obtained in vitro using bioregulators of microbiological origin. Curr. Chem. Biol. 13, 7389. DOI : 10.2174/2212796812666180507130017 (ISSN 1872-3136 (Online), ISSN 2212-7968 (Print). (Indexed in Scopus)
  • Blyuss K.B., Fatehi F., Tsygankova V.A, Biliavska L.O., Iutynska G.O., Yemets A.I. and Blume Y.B. (2019). RNAi-Based Biocontrol of Wheat Nematodes Using Natural Poly-Component Biostimulants. Front. Plant Sci. 10: 483. doi: 10.3389/fpls.2019.00483. (Impact Factor 4.298 (2016), 3.677 (2017), Indexed in Web of Science and Scopus).
  • Adekunle Odunayo Adejuwon, Victoria Anatolyivna Tsygankova, Abiola Muhammad Adeosun, Adefemi Olawale Falase, Olubunmi Sharon Obayemi, Fatai Ishola Amusa. Phytochemical screening and antimicrobial efficacy of the root bark of Securidaca longipedunculata extracts. AMERICAN JOURNAL OF RESEARCH IN MEDICAL SCIENCES. 2019. Vol. 5, No 1, P. 7 13. doi: 10.5455/ajrms.20181204113428.


Our team. Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Compounds.
Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, 2011.

Esma Abdurakhmanova PhD Thesis defense. Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Compounds. Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, 2017.