COST INFORMATION DAYS SOFIA, 24-25 OCTOBER 2013 - Hotel Sofia

1. COST INFORMATION DAYS SOFIA, 24-25 OCTOBER 2013 - Hotel Sofia

2. New Drugs for Neglected Diseases   Management Commettee Chair: Leopold Flohé Vice chair: Theodora Calogeropoulou Science officer: Erwan Arzel, Administrative officer: Svetlana Voinova

3. On July, 30th, 2008, the new Cost-CM0801 Action on "New Drugs for Neglected Diseases" has officially started by the signing of the memorandum of understanding by 15 countries. •    Belgium (2) •    Bulgaria (2) •    Finland (2) •    France (2) •    Germany (2) •    Greece (2) •    Israel (1) •    Italy (3) •    Lithuania (1) •    Norway (2) •    Poland (1) •    Portugal (2) •    Slovenia (1) •    Spain (2) •    Sweden (3) •    Switzerland (2) •    United Kingdom (3)

5. Working groups  of the project Kick-off meeting of the management committee, 28 November, 2008, Brussels, Belgium.

6. New Drugs for Neglected Diseases   2008-2012 PURPOSES: Development of novel drugs to treat neglected diseases such as African sleeping sickness, Chagas disease and Leishmaniasis. Coordination between related approaches of molecular genetics, biochemistry, medicinal chemistry, crystallography and bioinformatics and complementation with industrial experience. Identification of the drug targets essential to the parasites but absent or different in the host, using the established genomes of the parasites, since inhibitors thereof hold promise as safe and efficacious therapeutics. To validate drug targets as tools in drug discovery processes using complementary strategies

7. New Drugs for Neglected Diseases   2008-2012 STRATEGIES: i) high-throughput screening of natural product and other compound libraries and ii) in silico screening of virtual libraries to identify novel leads; iii) chemical synthesis and optimization of identified leads; and iv) structure-based inhibitor design based on established structures or molecular models. The potential therapeutic profile of novel compounds active in vitro will be worked out by techniques of high prognostic value in respect to drug safety. The most promising compounds will be tested in established infection models for all the diseases to choose the most attractive candidates for preclinical and clinical development. The Action members will cover all expertises required for the multidisciplinary early drug discovery phase.

8. CM0801: New drugs for neglected diseases Activities . Kick-off meeting of the management committee, 28 November, 2008, Brussels, Belgium. 10th Drug Development Seminar in conjunction with the COST Action CM0801 2009, Rauischholzhausen Castle, Marburg, Germany 18 – 20 March, 2009 Second Annual Meeting CM0801, Siena, Italy, from May 28th – 30th, 2010, Certosa di Pontignano 42nd Microsymposium ‘Glycosomes, trypanosomatid metabolism and drug discovery’ and COST Expert Meeting ‘Drugs for Neglected Diseases’, 28-29 October, 2010 WG1/ WG3 expert meeting, South-West University, Bulgaria, 29-31 May, 2009 WG2/ WG4 expert meeting, London, UK, Sept 21-22, 2009

9. Short technical and scientific missions The aim of a Short-Term Scientific Mission (STSM) is to contribute to the scientific objectives of the Action. These Missions (Exchange Visits) are aimed at strengthening the existing network by allowing scientists to go to an institution or laboratory in another COST Country to foster collaboration, to learn a new technique or to take measurements using instruments and/or methods not available in their own institution/laboratory. They are particularly intended for young scientists.

10. STSM missions and Bulgarian participations Tatiana Dzimbova, Training School on "In silico tools for prioritization of drug targets". Certosa di Pontignano - Siena, Italy May 16nd – 21th 2011 . Report “PNA-Synthesis, Properties and Applications”. Qualification - docking molecular modeling Ivan Trenchev, Training School and Workshop VIII EWDD Eighth European Workshop in Drug Design, Certosa di Pontignano - Siena, Italy May 22nd – 28th 2011 Poster „Integer programming approaches to HP folding“ N. Yanev, P. Milanov, I. Trenchev, I. Mirchev – Qualification & prediction of 3D structure of the chemical compounds ADUN – software NAMD – installed in SWU GOLD -

11. STSM missions and Bulgarian participations Tatiana Dzimbova, Training School of the COST Action CM0801 on “New Drugs for Neglected Diseases” – Enzyme purification and screening methods in drug discovery. 28 November – 3 December 2011, Modena, Italy. – Isolation and purification activity

12. SOFTWARE PACKAGES INSTALLED AND USED IN SOUTH-WEST UNIVERSITY IN BLAGOEVGRAD 1. DOCKING AND MOLECULAR MODELING MOE - Molecular operating environment; homology modeling of 3D models of different types of organic compounds and QSAR AVOGADRO (Amedeo Avogadro|) - contemporary pharmacophore-generating platform for description and visualization of organic molecules. GOLD (Genetic Optimisation for Ligand Docking) - docking MOLEGRO: Molecular viewer and Virtual docker GAUSSIAN – 3D structure modeling AUTODOCK - ligand-target interactions and AUTOGRID VMD (Visual Molecular Dynamics) EMBOSS (European Molecular Biology Open Software Suite)

13. 2. PREDICTION OF 3D STRUCTURE OF CHEMICAL COMPOUNDS ADUN – free molecular simulator for: computer biophysics, biochemistry, bioinformatics; distribution - under GNU Public License NAMD - Not (just) Another Molecular Dynamics program – for highly parallel computing, suitable for large molecules;

14. STSM missions and Bulgarian participations Tatiana Dzimbova, 9th Annual Meeting of Bioinformatics Italian Society (BITS) from May 2-4, 2012. Catania, Italy poster „Computer modeling of human delta opioid receptor“, F. Sapundzhi, T. Dzimbova, N. Pencheva, P. Milanov – Radoslav Mavrevski, Training School of the COST Action CM0801 on “New tools for drug design” October 15 – 20 2012, Certosa di Pontignano - Siena, Italy Fatima Sapundji, Training School of the COST Action CM0801 on “New tools for drug design” 15 – 20 October 2012, Certosa di Pontignano - Siena, Italy

15. CM0801: New drugs for neglected diseases Activities . In silico tools for prioritization of drug targets, May 16-21, 2011, Siena, Italy, Training School of the Working Group 1 Third Annual Meeting CM0801. Topic : Medicinal Chemistry in Parasitology, 2011. Modena, Italy, from 5-7 October 2011 4th Annual Meeting of Action CM0801 "New Drugs for Neglected Diseases", September 19-21, 2012 at Kolymvari, Crete COST Action CM0801 Training School on “In silico tools for drug discovery” , 15-20 October 2012, at Siena, Italy Training School of the COST Action CM0801 on “New Drugs for Neglected Diseases. Modena, Italy 28 November - 3 December, 2011 WG3 meeting 2012 is organized by Maurizio Botta at Certosa di Pontignano as adjunct meeting of the IV EWDSy (European Workshop in Drug Synthesis;

16. OUR OBJECTS: Trypanothione synthetase-amidase TrS-A Spermidine analogues as inhibitors of TrS-A Mu – opioid receptor as target; docking with theoretical models and with crystallographic forms (Molegro) -kyotorphins - endogenous enkephalins - enkephalin analogues Delta-opioid receptor – as a target for enkephalin analogues, substituted with Cys2.

17. Publications: T. Dzimbova, R. Mavrevski, N. Pencheva, T. Pajpanova, P. Milanov (2012) Computer modeling of ligand-receptor interactions – enkephalin analogues and delta-opioid receptor. Bulgarian Chemical Communications 44 (3) 242-245. (IF 0.320) ISSN 0324-1130 Tatyana Dzimbova, Fatima Sapundzhi, Nevena Pencheva, Peter Milanov (2012) Computer modeling of human μ-opioid receptor. Peptides 2012:Proceedings of the 32nd European Peptide Symposium, George Kokotos, Violetta Constantinou-Kokotou, John Matsoukas (Editors), 232-233. ISBN 978-960-466-121-3 Tatyana Dzimbova, Fatima Sapundzhi, Nevena Pencheva, Peter Milanov (2013) Computer Modeling of Human Delta Opioid Receptor. Int. J. Bioautomation 17 (1) 5-16 ISSN 1314-2321 (on-line)

18. Thank you