COST INFORMATION DAYS SOFIA 24 -25 OCTOBER 2013

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

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

On July, 30 th, 2008, the new Cost-CM 0801 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)

Working groups of the project Working groups Chairs • Kick-off meeting of the management committee, 28 November, 2008, Brussels, Belgium. Working Group 1 (WG 1), “Molecular biology of pathogenic Trypanosomatidae” Working Group 2 (WG 2), “Standardisation of Compound Documentation” Working Group 3 (WG 3), “Structural Biology and Medicinal Chemistry” Working Group 4 (WG 4), “Coordination and Harmonisation of Efficacy Evaluation” Helena Castro Achiel Haemers Elisabeth Davioud. Charvet Dr. Vanessa YARDLEY

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

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

CM 0801: New drugs for neglected diseases Activities . • • Kick-off meeting of the management committee, 28 November, 2008, Brussels, Belgium. 10 th Drug Development Seminar in conjunction with the COST Action CM 0801 2009, Rauischholzhausen Castle, Marburg, Germany 18 – 20 March, 2009 • • WG 1/ WG 3 expert meeting, South-West University, Bulgaria, 29 -31 May, 2009 WG 2/ WG 4 expert meeting, London, UK, Sept 21 -22, 2009 • Second Annual Meeting CM 0801, Siena, Italy, from May 28 th – 30 th , 2010, Certosa di Pontignano • 42 nd Microsymposium ‘Glycosomes, trypanosomatid metabolism and drug discovery’ and COST Expert Meeting ‘Drugs for Neglected Diseases’, 28 -29

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.

STSM missions and Bulgarian participations Tatiana Dzimbova , Training School on "In silico tools for prioritization of drug targets". Certosa di Pontignano Siena, Italy May 16 nd – 21 th 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 22 nd – 28 th 2011 Poster „Integer programming approaches to HP folding“ N. Yanev , P. Milanov , I. Trenchev , I. Mirchev – Qualification & prediction of 3 D structure of the chemical compounds • ADUN – software NAMD – installed in SWU • GOLD •

STSM missions and Bulgarian participations • Tatiana Dzimbova , Training School of the COST Action CM 0801 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

SOFTWARE PACKAGES INSTALLED AND USED IN SOUTH-WEST UNIVERSITY IN BLAGOEVGRAD 1. DOCKING AND MOLECULAR MODELING • MOE - Molecular operating environment ; homology modeling of 3 D 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 – 3 D structure modeling • AUTODOCK - ligand -target interactions and AUTOGRID • VMD (Visual Molecular Dynamics) • EMBOSS (European Molecular Biology Open Software Suite)

2. PREDICTION OF 3 D 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 ;

STSM missions and Bulgarian participations • • • Tatiana Dzimbova , 9 th 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 CM 0801 on “New tools for drug design ” October 15 – 20 2012, Certosa di Pontignano - Siena, Italy Fatima Sapundji , Training School of the COST Action CM 0801 on “New tools for drug design ” 15 – 20 October 2012, Certosa di Pontignano - Siena, Italy

CM 0801: 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 • CM 0801. Topic : Medicinal Chemistry in Parasitology , 2011. Modena, Italy, from 5 -7 October 2011 Training School of the COST Action CM 0801 on “New Drugs for Neglected Diseases. Modena, Italy 28 November - 3 December, 2011 WG 3 meeting 2012 is organized by Maurizio Botta at Certosa di Pontignano as adjunct meeting of the IV EWDSy (European Workshop in Drug Synthesis; • 4 th Annual Meeting of Action CM 0801 "New Drugs for Neglected Diseases", September 19 -21, 2012 at Kolymvari, Crete • COST Action CM 0801 Training School on “In silico tools for drug discovery” , 15 -20 October 2012, at

OUR OBJECTS: Trypanothione synthetase-amidase Tr. S-A Spermidine analogues as inhibitors of Tr. S-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 Cys 2.

Publications: T. Dzimbova, R. Mavrevski, N. Pencheva, T. Pajpanova, P. Milanov (2012) Computer modeling of ligandreceptor interactions – enkephalin analogues and delta-opioid receptor. Bulgarian Chemical Communications 44 (3) 242 -245. (IF 0. 320) ISSN 03241130 Tatyana Dzimbova, Fatima Sapundzhi, Nevena Pencheva, Peter Milanov (2012) Computer modeling of human μ-opioid receptor. Peptides 2012: Proceedings of the 32 nd European Peptide Symposium, George Kokotos, Violetta Constantinou. Kokotou, John Matsoukas (Editors), 232 -233. ISBN 978960 -466 -121 -3 Tatyana Dzimbova, Fatima Sapundzhi, Nevena Pencheva, Peter Milanov (2013) Computer Modeling

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