Proposal project characterization:
The project is directed for development of preparative methods synthesis of new antimicrobial, fungicidic and grown regulative compounds on the basis of thio-, thiosulfoderivatives of quinones and heterocycles, for establishment of their structure, for study of physical and chemical properties and biological action of the synthesized compounds.
The using of methods of computer-calculations is planned in work with bringing in the internet on-line software for establishing a connection "structure-activity" and prediction of possible spectrum of their physiology action and level of toxicity. On the basis of biological screening among synthesized new tio-, thiosulfoderivatives of quinone and heterocycles will establish "compounds-leaders" for which on the basis of theoretical and practical results directions of subsequent experimental biological researches will be certain
The aims of our research are:
- Synthesis of heterocyclic, including of phenothiazinic derivatives of different structure.
- Synthesis of sulfurcontaining naphthoquinones (thiols, sulfides, sulfenamides, sulfonic acids, sulfones, sulfoxydes and others like that).
- Synthesis of thiosulfonatic derivatives: thiosulfonic acids and their salts, S-esters of thiosulfonic acids with heterocyclic, carbocyclic, aliphatic, functionally substituted aliphatic and aromatic substitutes in sulfonyl and thiol fragments.
- Biological researcher of the synthesized compounds on antimicrobial, fungicidic, grown regulative activity.
The scope of researches within the framework of this project will be new biologically active heterocyclic, including of phenothiazinic, sulfur-containing naphthoquinonic and thiosulfonatic derivatives. The object of work will be an organic synthesis, study of chemical, spectral, biological properties of phenothiazine, thiocontaining naphthoquinonic and thiosulfonic derivatives.
The terms of carrying out of reactions will be optimized (temperatures of reactionary mixture, correlation of components and others like that) for development of preparative methods of obtains of new biologically active compounds. For establishment and confirmation of structure of the synthesized compounds the followings methods of researches will be applied: organic synthesis, spectral methods (NMR, IR, UV spectroscopy), element analysis, quantum-chemical calculations, computer and experimental biological screening.
Present-day level of knowledge and experience in the proposed research topic.
Intensive development of chemistry of sulfurcontaining organic compounds, in particular those, which contain sulfur in the different degrees of oxidation, and also group SO2-S in combination with naphthoquinonic, heterocyclic fragments, including of phenothiazinic, is predefined by their important scientific and practical value. Among sulfurcontaining compounds are found preparations with antiinflammatory, bactericidal, antiviral, antitumor, gerbicidic, fungicidic, insecticidic, grown regulative activity and others like that. Large quantity of quinone’ derivatives and also thisulfonatic derivatives show bacteriostatic, bactericidic, fungicidic, insecticidic activity. Compounds are higher mentioned are offered as antiviral, antituberculous, antitumor, antimicrobial, anthelmintic antimalarial preparations for treatment of different types of diseases. Preparations on the basis of derivatives of 1,4-naphtoquinone are effectively used for treatment of disorders of functions of cerebrum (cerebral heart attack, hemorrhage of cerebrum, atherosclerosis), and also have high antioxidative, cytolitic and cytostatic activity. It is known that at the prolonged using of antibacterial and a fungicidic medication the sensitiveness of microorganisms is diminishes, that causes the necessity of update of assortment of these preparations. Confirmation of this fact is rise of problems at treatment of different infectious diseases.
Research of new compounds on grown regulative activity is related with the search of facilities of increase of the productivity and quality of rural-economic products. New antioxidants and growth regulators are important not only for the increase of efficiency of production of rural-economic goods, but also with the purpose of providing of population high-quality ecologically safe food stuffs, sterns for a stock-raising. That is why a search of new biologically active compounds is among sulfurcontaining of naphthoquinone derivatives and different heterocyclic compounds with high antimicrobial, fungicidic and grown regulative activity is actual direction of developments.
The list of publications according to the level of knowledge in this research topic:
1. (E)-3-(2-Alkyl-10H-Phenothiazin-3-yl)-1-arylprop-2-en-1-ones: Preparative, IR, NMR and DFT Study on their Substituent-Dependent Reactivity in Hydrazinolysis and Sonication-assisted Oxidation with Copper(II)-nitrate
Luiza Gaina, Antal Csámpai, György Túrós, Tamás Lovász, Virág Zsoldos-Mády, Ioan A. Silberg and Pál Sohár, accepted at Eur. J. Org Chem. 2006
2. Substrate-Selective formation and Structure Elucidation of Chalcones containing Ferrocene and phenothiazine units, T. Lovasz, G. Turos, L. Gaina, A. Csampai, D. Frigyes, B. Fabian, I. Silberg, P. Sohar, J. Molecular Structure, 2005, 751, 100-108
3. Csámpai, A., Abrán, Á., Kudar, V., Túrós, Gy., Wamhoff, H., Sohár, P.: Synthesis, NMR, IR spectroscopic and X-ray study on novel [pyridazin-3(2H)-one-6-yl]ferrocenes and related ferrocenophanes. J. Organomet. Chem., 2005, 690(3), 802-810.
4. Nagy, T. Zs., Csámpai, A., Kotschy, A.: Ferrocenyl-palladium complexes in cross-coupling reactions: a comparative study Tetrahedron, 2005, 61, 9767-9774.
5. Difluorenylsilanes, -germanes, and -stannanes Exhibiting an Unprecedented Parallel Arrangement of the Fluorene Units. Nemes, Gabriela Cretiu; Silaghi-Dumitrescu, Luminita; Silaghi-Dumitrescu, Ioan; Escudie, Jean; Ranaivonjatovo, Henri; Molloy, Kieran C.; Mahon, Mary F.; Zukerman-Schpector, Julio, Organometallics, 2005, 24, 1134-1144
6. Tin(IV) halide complexes of AsPh3: The structures of trans-SnCl4(AsPh3)2 and SnBr4(AsPh3)AsPh3. Mahon, Mary F.; Moldovan, Natalia L.; Molloy, Kieran C.; Muresan, Alexandra; Silaghi-Dumitrescu, Ioan; Silaghi-Dumitrescu, Luminita, Dalton Transactions, 2004, (23), 4017-4021
7. A Density functional Theory of Distortions from Octahedral Symmetry in Hypoelectronic Six-Vertex Polyhedral Clusters of the Group 13 Elements Boron, Indium, and Thallium
R.B.King, I.Silaghi-Dumitrescu, A. Kun, in Group 13 Chemistry: From Fundamentals to Applications. Eds. P.J.Shapiro and D.A.Atwood, American Chemical Society Symposium Series 822, American Chemical Society, Washington, D.C. (USA) 2002, Chapter 15, pp.208-225.
8. A convenient route to 1,4-dihydro-3-cyano-10-methyl-pyrido[3,2-g]-quinoline derivatives as key-intermediates for the synthesis of novel MDR reversal agents.”
C. Moldovan , Castelia Cristea , I. A. Silberg , A. Mahamoud , C. Deleanu and J. Barbe .
Heterocyclic Communications, 2004, 10 (1), 19-24.
9. “Microwave-assisted synthesis of phenothiazine and quinoline derivatives”
L. Gaina,, Castelia Cristea , C. Moldovan , D. Porumb, E. Surducan, C. Deleanu, A. Mahamoud , J. Barbe and I. A. Silberg .
Int. J. Mol. Sci., 2007, 8, 70-80.
10. “Coordination compounds of copper(II) with new 1,4-benzothiazino-[2,3-b]-phenothiazine derivatives”,
L. Ghizdavu, Castelia Cristea, I. A. Silberg, C. Bălan, L. David
Synthesis and Reactivity in Inorganic and Metal-organic Chemistry, 2002, 32 (1), 1-7.
11.”Sulfur-Containing Derivatives of 1,4-Naphthoquinone, Part 1: Disulfide Synthesis”
M. V. Stasevych, M. Yu. Plotnikov, M.O. Platonov, S.I. Sabat, R.Ya. Musyanovych and V.P.Novikov
Heteroatom Chemistry 2005, 16 (3), 205-211
12. ”Sulfur-Containing Derivatives of 1,4-Naphthoquinone, Part 2: Sulfenyl Derivative Synthesis”
M. V. Stasevych, M.Yu. Plotnikov, M.O. Platonov, S.I. Sabat, R.Ya. Musyanovych and V.P.Novikov
Heteroatom Chemistry 2005, 16 (7), 587-598
13. „Syntesis and antimicrobial evaluation of novel 2-substituted-3-mercapto-1,4-naphthoquinones”
M. V. Stasevych, V.G. Chervetsova, M.Yu. Plotnikov, M.O. Platonov, S.I. Sabat, R.Ya. Musyanovych and V.P.Novikov
Ukrainica Bioorganica Acta 2 2006, 33-49
14. „Facile synthesis of 2,3-phthaloylpyrocoline-1-carboxylic acid and its new deivatives”
M. V. Stasevych, M.Yu. Plotnikov, M.O. Platonov, S.I. Sabat, R.Ya. Musyanovych and V.P.Novikov
Ukrainica Bioorganica Acta 2 2007, 39-43
15. „Sulfennaphthoquinones”
M. V. Stasevych, M. Semenjuk, I. Mandzya, M.Yu. Plotnikov, R.Ya. Musyanovych and V.P.Novikov
Chemistry &Chemical technology, 2007, Vol. 1, No. 1, 35-40 |