Projects / Programmes
Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin (Slovene)
January 1, 2009
- December 31, 2014
| Code |
Science |
Field |
Subfield |
| 1.09.00 |
Natural sciences and mathematics |
Pharmacy |
|
| 1.04.00 |
Natural sciences and mathematics |
Chemistry |
|
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Researchers (57)
Organisations (1)
Significance for science
Importance of the proposed research programme for the development of science resides in discovery of novel bioactive compounds with a potential for development to drugs in important therapeutic areas and in (ii) development of methods for their design, synthesis and mechanism of action studies at molecular level. In the period from 2009 till 2014 the research programme importantly contributed to discovery of innovative antibacterial agents with new mechanisms of action (MurA-F inhibitors, D-Ala-D-Ala ligase inhibitors, D-aspartate ligase inhibitors, inhibitors of transglycosylase and transpeptidase domains of penicillin-binding proteins, gyrase B and topoisomerase IV inhibitors) which is a big challenge for science worldwide due to increasing resistance of bacteria to currently used antibacterial drugs. Glycomimetic DC-SIGN receptor (lectin involved in recognition and elimination of bacteria in early infection phases) antagonists with high binding affinity in comparison to D-manose are an important contribution to discovery of novel antibacterial agents. The results obtained in DC-SIGN field offer an opportunity for establishing a spin-off company. A high worldwide incidence of cardiovascular and thrombotic diseases which is especially threatening in developed countries requests an intensive search for new antithrombotics. The research programme results in application of a concept of designed multiple ligands to discovery of novel antithrombotic agents (thrombin inhibitor/ fibrinogen receptor antagonist, factor Xa inhibitor/fibrinogen receptor antagonist) could provide the basis for antithrombotic agents of the future. Application of up to date genomic technologies, interdisciplinary approach and intensive international cooperation of the research programme enabled successful identification of new proapoptotic molecules. Understanding the mechanisms of apoptosis regulation and successful modulation of this process will pave the way to more rational design of new anticancer drugs interfering with the process of apoptosis. The identified low molecular weight 17ß-hydroxysteroid-deyidrogenase (17-HSD) and aldo-keto-reductase AKR1C1-AKR1C4 inhibitors possess a potential for further development towards drugs for treatment of hormone-dependant cancers. The developed new molecular tools for EPR spectroscopy and fluorescence microscopy/ spectroscopy are an important contribution to mechanism-of-action studies of various molecules and processes (apoptosis induction, studies of membrane domains, transmembrane signalling). The identified novel catepsin H and L inhibitors, NOD1 and NOD2 agonists and antagonists, novel modulators of voltage-gated sodium channels and PXR antagonists, inhibitors of butyrylcholine esterase – an important target involved in pathology of Alzheimer disease and FimH (adhesive receptor for carbohydrates) ligands are all important contributions to drug discovery in different therapeutic areas. The importance of results of the research programme for science in the period 2009-2014 is thus in - discovery of novel enzyme inhibitors and modulators of receptors as novel antibacterial, antithrombotic and antitumor agents with potential for further development in pharmaceutical industry - application and development of a paradigm of designed multiple ligands in the discovery of antibacterial, antithrombotic and antitumor drugs - identification of new target macromolecules involved in regulation of apoptosis and discovery of new apoptosis modulating compounds - new approaches to the design of multiple ligands - new approaches to rational drug design and drug synthesis - development of new synthetic methods - development of new mimetics of peptides, sugars and lipids - development of new molecular tools for study of biological processes and biological macromolecules
Significance for the country
Discovery of novel innovative drugs and introducing them to the market in cooperation with strategic partners is a way to assure a sustained growth to Slovenian pharmaceutical industry which is currently one of major players in the Slovenian economy. The current generic nature of the Slovenian pharmaceutical industry does not preclude its evolution into research-oriented pharmaceutical industry and education of creative and competent scientists in research programme such as this one importantly contributes to this important socio-economic task. In the period from 2009 till 2014 the research programme generated new and mastered the existing knowledge both of which are of paramount importance for sustained development of pharmaceutical industry and drug – oriented research in Slovenia. Although the major part of results of the completed research programme period can be regarded as precompetitive research results which provide valuable new knowledge on therapeutic modulation of selected drug targets involved in different pathological processes, important for development of new drugs in innovative pharmaceutical industry, some results, protected by awarded patents, have a potential of their direct application for new drug development in pharmaceutical industry on a competitive level through licensing. Novel bioactive compounds with a high potential for development to lead compounds and drugs resulting from the research programme can be a good starting point for development of innovative medicines in cooperation of the Slovenian and international pharmaceutical industry. The results related to development of alternative synthetic procedures, protected by several patent applications, find their direct application in Slovenian generic pharmaceutical industry. Several awarded national patents provide a basis for commercialization of some products of plant origin by a Slovenian private company. Some results of the research programme have reached a level of technological maturity which will enable founding of a spin-off company. Information gained on the occurrence and harmful effects of some chemicals on human health are a very important contribution to the preparation of guidelines, directives and regulations for the harmonized assessment and risk management at national and European level, which will significantly contribute to the protection of public health. Young scientists educated in the past research programme period will gain competences for autonomous creative work in pharmaceutical industry, where they will create novel research focuses. They are perfectly trained for research work at universities, other research institutes and governmental agencies. Twenty-six successfully completed doctorates mentored by the research programme team members prove this concept as one of major socio-economic achievements of the research programme in the past and are a guarantee for prosperity in the future. Fostering scientific excellence was one of major goals of the research programme, contributed to affirmation of Slovenian science through publications in leading scientific journals and participation at most important international scientific conferences worldwide. A broad network of international collaborations which are an important attribute of the research programme is a good way for promotion of Slovenian science and establishing strategic alliances for the benefit of Slovenian and global science. All these activities contribute to creation and preservation of the country's national identity in Europe and in the world. Dissemination of results of the research programme to students and general population through media as one of priority outreach activities of the research programme team contributed to popularization of science among young people and in the society.
Most important scientific results
Annual report
2009,
2010,
2011,
2012,
2013,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
2012,
2013,
final report,
complete report on dLib.si
