Projects / Programmes
Synthesis of novel ruthenium compounds and their potential use in electrochemotherapy of tumors
| Code |
Science |
Field |
Subfield |
| 1.04.00 |
Natural sciences and mathematics |
Chemistry |
|
| Code |
Science |
Field |
| P360 |
Natural sciences and mathematics |
Inorganic chemistry |
ruthenium compounds; anticancer metallodrugs; electroporation; in vivo tests
Researchers (10)
Organisations (3)
Abstract
The proposed interdisciplinary project brings together experts from fields of chemistry, electrical engineering, biology and medicine with the aim to work in synergy on developing electrochemotherapy with ruthenium compounds. Electrochemotherapy is an efficient local treatment for solid tumors which is in clinical use since 2006 and has excellent response results. In addition, clinical tests for some of ruthenium compounds as potential anticancer agents are also already in progress.The main aims of this work are: Chemical synthesis and characterization. Isolation of new ruthenium compounds and their characterization by different physico-chemical methods. Use of various ligands (triazoles, quinolones, N,N-ligands, purines, acridines, coumarines) to get the new potential antitumor metallodrugs with requested properties.
In vitro cytotoxicity determination. Screening of anticancer potential in vitro for selected compounds should reveal the best candidates for further electroporation experiments. Selected compounds will be tested alone and combined with electroporation in order to establish whether electroporation can potentiate antitumour effectiveness of ruthenium compounds in vitro.
In vivo electrochemotherapy tests. In the last phase of the project in vivo tests on animal tumor models will be performed. Evaluation of possible antitumor effectiveness of electrochemotherapy might offer new effective drugs for use in electrochemotherapy (in addition to cisplatin and bleomycin that are already used).
The results of this project will reveal if combination of systemic administration of ruthenium compounds and electroporation is suitable to be used in cancer treatment and could be further developed for use in clinical practice.
Significance for science
The chemical part of the project which contains the isolation and characterization of novel ruthenium coordination compounds is important from several reasons. Syntheses of novel compounds lead to better understanding of metal complex formation and mechanisms of reactions. Characterization data give us a view into their physico-chemical properties which may be interesting for different applications. All new structural data are stored in databases (such as Cambridge Structural Database (CSDB)) and are accessible to researchers all over the world for their scientific work. It is crucial to understand the relation between structure and properties of matter (biological, physical, chemical and other) for better understanding of its biological activity. Based on structure-activity relationships (SAR) scientists try to modify the effect or the potency (i.e. activity) of bioactive chemical compounds by modifying their chemical structure. It is known that some ruthenium compounds exert anticancer activity but the details of these processes are not known. It would be important to understand how the ligands coordinated to the metal affect the activity of the complex. A long term aim of these efforts is a rational preparation of compounds with known applicable properties (e.g. new drugs). Two ruthenium compounds are already tested in the clinical trials (phase II.) and many others are used in preliminary tests. Due to their anticancer properties, ruthenium compounds are also interesting for pharmaceutical industry. It is our aim to show that multidisciplinary approach (isolation of novel ruthenium compounds, testing of its effects in combination with electroporation in vitro and in vivo) could be suitable for the treatment of certain cancer diseases. In these tests our novel compounds are used as well as ruthenium compounds that are already used in clinical trials (provided by our foreign collaborators).
Significance for the country
Our project is harmonized with national Research and Development Programme for funding research priorities because it deals with new materials, procedures and technologies. On the other hand this research is also aimed to improve health and quality of life.
Our research may lead to development of practical applications (e.g. chemical, pharmaceutical industry, cancer treatment etc.). The development and testing of new ruthenium compounds may result in a possible economic exploitation. We carefully follow applicability of new results and if necessary intellectual property will be protected. During this project we have actually also discovered that the racemization of nicotine could be provoked with ruthenium compounds and we have protected this procedure by a patent application.
In our project foreign researchers from the neighbouring countries (Italy, Austria) are involved, from this reason the project is also important for further development of regional cohesion and cooperation within CEI (Central European Initiative) countries and AAD (Alps Adria Danube) region. This type of international cooperation with other academic institutions brings the involvement in European higher education and research area. We also cooperate with the same partners in other projects (COST D39, SLO-AUT bilateral) and we can clearly say that collaboration is now stronger. Last year Professor I. Turel was on a monthly study visit of the labs of Prof. B.K. Keppler in Vienna and in 2010 more exchange visits (1-2 months) were realized. Ph.D. student J. Kljun has visited the labs of Prof. B.K. Keppler in Vienna (through COST STSM system) and I. Bratsos (from the group of E. Alessio) has visited the labs of I. Turel. The results generated and collaboration further advanced within the proposed project will clearly increase our possibilities to successfully participate in new European Programmes which is further important from national point.
It is also very important for further development of our country that several under- and postgraduate students are involved in our practical work. Through this, knowledge and experiences are transferred to younger scientists who are in constant contact with domestic and excellent foreign laboratories. These experiences can later be successfully used in their professional careers. Additionally, our research is related to numerous programmes of our graduate and postgraduate study at University of Ljubljana which enables the students to connect their theoretical knowledge with practical. It is also worth to mention that in 2009 the group of professor D. Miklavčič has traditionally organized International Scientific Workshop and Postgraduate Course (Electroporation based technologies and treatments) in Ljubljana. Doctoral student Rosana Hudej has presented the results of her work on effects of ruthenium compounds in combination with electroporation during this meeting.
Most important scientific results
Annual report
2008,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
