Bilateral Project, Modul III, Funded by ANCS, Program

Bilateral Project, Modul III, Funded by ANCS, Program

Bilateral Project, Modul III, Funded by ANCS, Program PN II Capacities Romania - Bulgaria Contract no. 43 / 13.06.2008 EVALUATION OF ANTITUMOR AND ANTIVIRAL ACTIVITIES OF NEWLY COORDINATION COMPOUNDS OF BILE ACIDS, SCHIFF AND MANNICH TYPE BASES WITH 3d METAL IONS Director: Dr. Luminita Patron Lenght: 13.06.2008 - 30.11.2009 ROMANIAN PARTNER Institution INSTITUTE OF PHYSICAL CHEMISTRY ILIE MURGULESCU, ROMANIAN ACADEMY Adress Phone/fax/e-mail Project leader Splaiul Independentei, nr. 202, Bucharest, 060021, Romania +40213167912 / +40213121147 / [email protected] Dr. Luminita Patron , Head of Coordination and Supramolecular Chemistry Colaborator: Institution INSTITUTE OF CHEMISTRY TIMISOARA Adress

Phone/fax/e-mail Responsible person Timisoara, strada Mihai Viteazu, nr. 24, Judetul Timis, cod postal 300223 +40256491818 / +40256491824 / [email protected] Dr. Otilia Costisor, Director FOREIGN PARTNER Institution INSTITUTE OF EXPERIMENTAL PATHOLOGY AND PARASITOLOGY, BULGARIAN ACADEMY OF SCIENCE (IEPP - BAS) Adress Phone/fax/e-mail Project leader Acad. Georgi Bonchev Str., Bl. 25, Sofia 1113, Bulgaria +35929793678 / +3592710107 / [email protected] Dr. Radostina Ivaylova Aleksandrova Research teams ROMANIAN PARTNER FOREIGN PARTNER INSTITUTE OF PHYSICAL CHEMISTRY ILIE MURGULESCU INSTITUTE OF EXPERIMENTAL PATHOLOGY AND PARASITOLOGY

Patron Luminita, PhD Culita Daniela Cristina, PhD Marinescu Gabriela, PhD Beteringhe Adrian, PhD Alexandrova, Radostina Ivaylova, PhD Alexandrov, Ivaylo Ivanov, DVM, PhD, DSc Alexandrov, Marin Tcviatkov, DVM, PhD Gabrashanska, Margarita Pavlova, DVM, PhD Simeonov, Konstantin Borisov, DVM, PhD Todorova, Iva Tomova Institute of Chemistry Timisoara Colaborators: Costisor Otilia, PhD Fagadar Cosma Eugenia, PhD Tudose Ramona, PhD Mosoarca Elena Maria, PhD student Vlad Mihaela, PhD student Bucovicean Carmen, PhD student Cretu Daniela master student Mot Corina master student Kalfin, Reni Emil, PhD (Institute of Neurobiology, BAS) LeventievaNecheva, Eleonora Vaniova (Institute of Neurobiology, BAS) Inchovska, Maya Petrova, PhD ((Institute of Experimental Morphology and Anthropology with Museum, BAS) Gluchcheva, Yordanka Georgieva PhD (Institute of Experimental Morphology and Anthropology with Museum, BAS)

Shishkov, Stoyan Angelov, PhD (Faculty of Biology, Sofia University St. Kliment Ohridski Genova, Petia Dinkova, PhD (National Centre of Infectious and Parasitic Diseases, Sofia, Bulgaria) Timcheva, Constanta Velinova, MD, PhD (National Specialized Hospital for Active treatment in Oncology, Sofia, Bulgaria) Consultant of the Project MSc Students from Faculty of Biology, Sofia University St. Kliment Ohridski PROJECT DESCRIPTION A general aim of the project presented here is the synthesis of new metal coordination compounds of transition metals with bile acids, Schiff and Mannich bases type ligands and the evaluation of their potential in vitro antitumor activities, as well as their antiviral properties. The knowledge concerning the relationship between the physical and chemical structure of the compounds and their antitumor and antiviral activities in vitro will be obtained. Such structure-activity informations will facilitate the design of drugs with improved anticancer or antiviral properties. The presented project is in accordance with the major priority topic HEALTH of the Seventh Framework Programme, aiming to improve the health of European citizens, and with the goals of the NATIONAL SCIENTIFIC STRATEGIES of Bulgaria and Romania. The joint work of Bulgarian and Romanian teams on the project will facilitate the exchange of ideas and research data, contacts between scientists of both teams, and will give an opportunity to prepare joint EU project in the future. The aim of the project presented here is the evaluation of cytotoxic and antiproliferative effects as well as antiviral activity of new synthesized coordination compounds of metals (Zn, Cu, Co, Fe, Ni, Pd, V) with bile acids, Schiff and Mannich bases type ligands. Project justification The need to find a safe and highly selective cure for neoplastic diseases remains a major challenge for modern science. The discovery of the antitumor efficacy of cisplatin and some related platinum complexes has stimulated the search for other metals with antineoplastic properties. Different metal complexes, including such of zinc, copper and cobalt, are found to be promising compounds for the design of new anticancer agents. We decided to investigate the antitumor and

antivirall properties of such namely compounds because of the following reasons: i)Zinc, copper, cobalt, iron and nickel are essential metals with broad spectrum of biological activities including DNA synthesis (Fe, Co), transport of oxygen, electrons, cell respiration (Fe), normal functioning of the immune and nervous system (Fe, Zn, Co, Cu), etc. ii)There are data about antineoplastic, antimicrobial and antiviral activities of different compounds containing these elements; iii)It was found in our previous investigations that some complexes of Zn(II), Cu(I, II), Co(II), Fe(II, III) and Ni(II) with various ligands (N,N-bis(4-antipyrylmethyl)-piperazine, N,N-tetra-(antipyryl-1-methyl)-1,2-diaminoethane, bile acids) expressed cytotoxic and antiproliferative effects on several animal and human tumor cell lines or exhibited antibacterial properties; iv)Numerous biological effects of the ligands have also been reported. The multiple physiological functions of bile acids are well known. Cholic acid, which belongs to bile acid family, and its semisynthetic analogs are reported to inhibit replication of human immunodeficiency virus type 1 (HIV-1) and are also used in the treatment of liver and gastrointestinal disorders. Furthermore, it has been suggested that bile acid conjugates could be helpful in the development of new approaches for targeted anticancer therapy. The cell cycle modulation and induction of apoptosis in several human cancer cells have been reported. Analysis of the objectives and foreseen benefits This project undoubtedly will also have a favourable educational and practical impact on young scientists, especially PhD and MSc students, post-docs and will influence for the best their research career. The joint work on the project presented here will facilitate the exchange of ideas and research materials, will give opportunities to prepare new EU projects in the future. The proposed objectives are targeting the optimal valorisation of scientific and high-level potential, the consolidation of an excellence Romanian Bulgarian research network. This project ensures the increase in visibility of the Romanian and Bulgarian science international scale, by publishing the results in ISI indexed journals. The proposed activities join together foundamental and applicative research and large-scale dissemination of the obtained results. The validity and the success chances of the project are revealed by the long-term partnership between the involved parties with the purpose of carrying research activities of great complexity from foundamental to applicative research. Diagram of project execution Year

2008 2009 Stage description (activities) Partner Synthesis and physico-chemical characterization of some coordination compounds of transition metal ions containing as ligands anions of bile acids. Romanian Synthesis and physico-chemical characterization of some coordination compounds of transition metal ions containing some Mannich bases as ligands. Romanian Evaluation of cytotoxic/antiproliferative and antiviral activities of the synthesized during the 1st year coordination compounds in cell cultures. Bulgarian Synthesis and physico-chemical characterization of some coordination compounds of transition metal ions containing as ligands Schiff bases and anions of bile acids. Romanian Synthesis and physico-chemical characterization of some coordination compounds of transition metal ions containing Mannich bases as ligands.

Romanian Evaluation of cytotoxic/antiproliferative and antiviral activities of the synthesized during the 2nd year coordination compounds in cell cultures. Investigations on the in vivo antitumor effect of the most promissing compound(s). Bulgarian Project budget Year 2008: 29 070 lei Year 2009: 31 398 lei Results: 1. Cobalt and cobalt compounds biological activity and potential antitumor properties, Radostina Alexandrova, Reni. Kalfin, Otilia Costisor, Luminita Patron, et.all., Proceedings of The second Edition of the Symposium New trends and strategies in the chemistry of advanced materials with relevance in biological systems, technique and environmental protection, 6-7 november 2008 Timisoara, Romania, pag.1-7. 2. The antimicrobial power of metals and metal compounds, Radostina Alexandrova, Ramona Tudose, Elena Mosoarca, Daniela Culita, Gabriela Marinescu, Proceedings of The second Edition of the Symposium New trends and strategies in the chemistry of advanced materials with relevance in biological systems, technique and environmental protection, 6-7 november 2008 Timisoara, Romania, pag. 36-42. 3. New heteropolinuclear complexes of Cu(II) and Zn(II) containing a pyrazolone derivative as ligand. Synthesis and spectral characterization, Elena Mosoarca, Ramona Tudose, Otilia Costisor, Proceedings of The second Edition of the Symposium New trends and strategies in the chemistry of advanced materials with relevance in biological systems, technique and environmental protection, 6-7 november 2008 Timisoara, Romania, pag.58-62. 4. Synthesis and characterization of 3d complexes with N,N-bis(antipyryl-4-methyl)piperazine, Ramona Tudose, Elena Mosoarca, Otilia Costisor, Proceedings of The second Edition of the Symposium New trends and strategies in the

chemistry of advanced materials with relevance in biological systems, technique and environmental protection, 6-7 november 2008 Timisoara, Romania, pag.75-79. 5. Eefectul combinatiilor complexe ale Co(II) cu ligand de tip baze Mannich asupra diviziunii mitotoce la Alium Cepa L, Ramona Tudose, Elena Mosoarca, Irina Petrescu, Otilia Costisor, Proceedings of The second Edition of the Symposium New trends and strategies in the chemistry of advanced materials with relevance in biological systems, technique and environmental protection, 6-7 november 2008 Timisoara, Romania, pag.217-220. 6. Coordination compounds of Co(II), Ni(II), Cu(II) and Zn(II) with ursodeoxycholic acid, Daniela C. CULI, Gabriela MARINESCU, Luminia PATRON, Floriana UN, Nicolae STANIC and Ma YUN, Revue Roumaine de Chimie, in press, 2009. 7. Spectral characterization and biological activity of Cu(II) complex containing N,N-tetra-(4-antipyrylmethyl)-1,2 diaminoethane (TAMEN) as ligand, Elena Maria Mosoarca, Ramona Tudose, Livia Avram, Mihai Milos, Carmen Bucovicean, Carmen Cretu, Corina Mot, Viorel Sasca, Radostina Alexandrova, Otilia Costisor, Proceedings of The Third Edition of the Symposium With International Participation New Trends and Strategies in the Chemistry of Advanced Materials, November 5-6, 2009 Timisoara, Romania, p. 139-142. 8. Copper Compounds as Possible Antitumor Agents, R. Alexandrova, R. Kalfin, E. Leventieva-Necheva, E.M. Mosoarca, R. Tudose, O. Costisor, D.C. Culita, G. Marinescu, L. Patron, Proceedings of The Third Edition of the Symposium With International Participation New Trends and Strategies in the Chemistry of Advanced Materials, November 5-6, 2009 Timisoara, Romania, p. 1-4. 6 Scientific Communications at National and International Scientific Meetings

Recently Viewed Presentations

  • CFCYFL YOUTH CAMP CFC Youth for Family and

    CFCYFL YOUTH CAMP CFC Youth for Family and

    LORD. 1. Share . an experience . or . area of . your. life . where you felt most loved by . God. 2. How can you respond to God's love for you? (Make specific resolutions)
  • Group 11 - UCF Department of EECS

    Group 11 - UCF Department of EECS

    Group 11. Motivation. Finding a parking spot in one of UCF's garages during rush hour is frustrating and time consuming. ... Apache 2 will be used as the http server. PHP and MySQL related modules will be loaded to facilitate...
  • World History

    World History

    The nuclear arms race and the development of the hydrogen bomb (1954). The US produced the first atomic bomb in 1945. The Soviet Union (USSR) soon developed their own. The US then developed a . hydrogen bomb (a thousand times...
  • Animal Farm - Yola

    Animal Farm - Yola

    Animal Farm is generally viewed as Orwell's critique of the communist system in the former Soviet Union. Significance Today But why - now that Soviet Communism has fallen and the Cold War is over -does Animal Farm deserve our attention?...
  • Christmas Storms and sunshine - Mr. Sadek's Classes

    Christmas Storms and sunshine - Mr. Sadek's Classes

    Christmas Storms and sunshine. Elizabeth CleghornGaskelll. Objectives . Analyze the impact of author choices. Analyze the impact of word choices. Initiate and participate in discussions. Demonstrate the command of the English language while writing.
  • Ethics: Discovering Right and Wrong

    Ethics: Discovering Right and Wrong

    Chapter Thirteen: Moral Realism and the Challenge of Skepticism Moral Realism This theory claims that moral facts exist and are part of the fabric of the universe: they exist independently of our thoughts about them
  • Sepsis 101 Colorado Hospital Association 2019 CHA Objectives

    Sepsis 101 Colorado Hospital Association 2019 CHA Objectives

    A Worldwide Problem. Sepsis is a major, world-wide health care problem . Affecting an estimated 30 million adults and children each year resulting in potentially six million deaths annually
  • Photography Composition using the Elements and Principles of Art

    Photography Composition using the Elements and Principles of Art

    Photography Content using the Elements and Principles of Art ELEMENTS are the basic building blocks Art Line Shape/Form Space Value Texture Color Emphasis Balance Unity Contrast Movement/ Rhythm Pattern/Repetition PRINCPLES of Art Elements The basic building blocks Line Shape/Form Space...