Metabolomics Workshop - Programa BIOTA/FAPESP
Transcrição
Metabolomics Workshop - Programa BIOTA/FAPESP
BIOTA/FAPESP Scientific Program for the 1st Semester, 2010 BIOprospecTA WORKSHOP International Workshop on METABOLOMICS IN THE CONTEXT OF SYSTEMS BIOLOGY: A RATIONAL APPROACH TO SEARCH FOR LEAD MOLECULES FROM NATURE Part of 2010´s Scientific Program of Biota + 10 FAPESP Carlos A. Joly (Coordinator of Biota Program) Célio Haddad Luciano verdade Mariana Cabral Vanderlan da S. Bolzani (Coordinator of the Workshop) February, 25-26, 2010 - FAPESP Auditorium Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 RESUMO DO PROJETO O projeto em pauta – International Workshop on METABOLOMICS IN THE CONTEXT OF SYSTEMS BIOLOGY: A RATIONAL APPROACH TO SEARCH FOR LEAD MOLECULES FROM NATURE tem como objetivo principal estabelecer discussões em torno de uma massa crítica de pesquisadores no Estado de são Paulo que atua em Química de Produtos Naturais, objetivando a pesquisa multidisciplinar de bioprospecção da biodiversidade remanescente no Estado, baseada nos últimos avanços do estado-da-arte das ciências químicas e biológicas. O Programa Biota, após 10 anos de existência, se organiza para novos desafios sobre a pesquisa multidisciplinar com a biodiversidade local, principalmente àquela voltada para o desenvolvimento sustentável das espécies que foram mapeadas nas áreas de Cerrado e da Mata Atlântica, ocorrentes no estado de São Paulo. O workshop foi idealizado dentro de uma nova filosofia da FAPESP, dedicada as discussões em temas relevantes dos Programas financiados por esta agência de fomento à pesquisa. Com forte componente transdisciplinar, este workshop trará avanços substanciais ao programa BIOTA-FAPESP, tendo em conta a temática científica escolhida para discussão durante os dois dias de discussão. As conferências que serão apresentadas fundamentam-se nos últimos avanços da química de produtos naturais e da farmacologia e permitirão um bom norteamento para a continuidade do Sub-programa BIOprospecTA para os próximos 10 anos. Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 ABSTRACT OF THE PROJECT The guideline project - International Workshop on Metabolomics IN THE CONTEXT OF SYSTEMS BIOLOGY: A RATIONAL APPROACH TO SEARCH FOR LEAD MOLECULES FROM NATURE has as main goal to enter into discussions around a critical mass of researchers in the State of São Paulo dedicated to the Chemistry Natural Products. The efforts to create a multidisciplinary research aimed at bioprospecting of remaining biodiversity in the state, based on the latest advances in state-of-the art of chemical and biological sciences will establish a new paradigm on the field of Natural Products dedicated to drug discovery. After 10 years, the Biota Program is being reorganized to reach new challenges, with a focus on multidisciplinary research on our biodiversity, especially those related to the species that have already been mapped in the areas of Cerrado and Atlantic Forest, of São Paulo. The workshop was designed within a new philosophy of FAPESP, dedicated to discussions on relevant topics of its Programs, which are being funded by this agency. With a strong interdisciplinary component, this workshop will bring substantial improvements to the BIOTA-FAPESP, taking into account the scientific field chosen for discussion during two days. All conferences will be presented by renowned researchers from USA, Europe and Brazil, based on the latest advances in natural products chemistry and pharmacology, and will contribute for the continuity of the Bioprospecta sub-program for the next 10 years. Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 The importance of the topic The focus on innovation in current drug discovery is one new targets, yet compound efficacy and safety in biological models disease – not target selection – are the criteria that determine which drug candidates enter to the clinic. Modern bioprospecting should consider a biology-driven approach to search for new drugs, which involves screening compounds by automated responses profiling in disease models based on complex human-cell systems. Drug discovery through cell systems biology could significantly reduce the time and cost of new drug development. Cell systems biology approach have been recently used to explore the potential implications of a drug discovery paradigm in which complex biological responses are used directly to screen for and select lead molecules. Recent studies suggest that primary human cell systems can be designed to model many aspects of disease biology, and robust, automated assays can be engineered to detect and discriminate a surprising breadth of disease-relevant pathways and mechanisms. Most of theses assays benefits from principles of systems biology, and mimic the complexity of disease process by incorporating multiple cell types and activating multiple pathways together. Objectives The main goal of this workshop is to show the last advances in the state-of-art of drug discovery, which has a practical approach to systems biology because this focus directly measure disease-relevant cellular responses without the need for complex in silico models whose application to predicting human cell responses, except in prescribed settings, is many years in the future. Most of today´s successful drugs are the chemical descendent of natural products or bioactive agents that were originally selected for their biological effects, and so far, Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 we have a fantastic source material to develop advance research aiming bioproducts (agrochemicals, fragrances, medicines and nutraceuticals) from the remaining Sao Paulo State biodiversity. The workshop will be held in to days: Background and Significance Certainly, the use of natural products has been the single most successful strategy in the discovery of novel medicines [Harvey, 2000]. Most of the medical breakthroughs are based on natural products, with for example, natural products as ligands for many of the known receptors and enzymes inhibition assays. In 1999, half of the top 20 best-selling drugs were natural products, and their total sales amounted to US$ 16 billions [Harvey, 2000]. The importance of natural products is evidenced by the new chemical entities (NCE) approved by regulatory authorities around the world in the past decade. Of the ca. 500 NCE, introduced in the period, nearly half are from natural resources [Cragg, 1997]. In 1999, the approval of the natural alkaloid galantamine as a medicine to treat Alzheimer’s disease shows that natural compounds from plants will continue to reach the market [Ferris, 2001]. The reasons for the continuous success of natural products as leads for drug development are several. First of all, because natural products are biosynthesized in natura to have an activity, e.g. as defense against microbial infections or predators, which means that the structures have drug-like properties that are selected during the evolution to bind to some target proteins in other organisms. A second reason – that seems – a chemical perspective, they are clearly different from what synthetic chemistry will achieve. The natural products are characterized by great structural complexity and obviously different and complementary to the synthetic compounds [Newman et al., 2003] Since the beginning of civilization, mankind has been exploring nature for medicines, as well as other applications. This has resulted, among others, in the discovery long ago of opium alkaloids (many antinociceptives based on morphine), cocaine (local Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 anesthetic), cinchone alkaloids (antimalarial compounds based on quinine), salicylic acid, and various tropane alkaloids contained in plants. (Newman et al., 2003). As can be learned from this review, the process continues in modern development and some examples are given (Table 1). In addition, ethnomedical plant-use data in many forms has been heavily utilized in the development of novel phytopharmaceuticals, providing a major focus in global health care, as well as contributing substantially to the drug development process, especially in developing countries [Farnsworth, 2000]. A major difference between the old times and present day drug development is probably that in the past, people tested the medicines directly on humans, whereas nowadays the starting point is a screening at molecular level, or in some cases on cellular level (e.g. antibiotics and antitumor compounds). This workshop deals with the most advanced in drug discovery sciences, and so far will bring a great contribution for the future of this important research area in Brazil. Table 1. Drugs of natural origin or derivatives that were on the market before synthetic drugsa,b. For some of these drugs, synthetic counterparts have not yet been developed*. Natural Compound Mode of Action Amphotericin B Artemisinin Atropine Avermectin Camptothecin Dicoumarol Digoxin Ecteinascidin 743 Ephedrine Ergocornine Fusidic acid Gentamycin Griseofulvin Harmaline Heparin Lovastatin Cell membrane permeability Interation with haem Muscarinic acetylcholine antagonist Cl- channel activator Topoisomerase I inhibitor Vitamin K antagonist Na+-K+-ATPase inhibitor Transcription factor antagonist β-adrenoceptor agonist Dopamine receptor agonist Interleukin antagonist Protein synthesis inhibitor Mitosis inhibitor MAO inhibitor Antithrombin III activator HMG-CoA synthetase inhibitor Morphine Paclitaxel Opioid receptor agonist Microtubule stabilization receptor Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 (Semi) synthetic drug Not yet described* Arthemether Butylscopolamine Selamectin Irinothecan Acenocoumarol Acetyldigoxin Not yet described* Isoprenaline Bromocryptine Not yet described* Metamycin Not yet described* Pargyline, deprenyl Not yet described* Simvastatin, pravastatin Pethidine, fentanyl Taxotere a Papaverin Penicillin G Physostigmine Podophyllotoxin Rampamycin Quinidine Salicilic acid Teprotide Tetracyclins ∆9-Tetrahydrocannabinol d-Tubocurarine Phosphodiesterase inhibitor Transpeptidase inhibitor Cholinesterase inhibitor Topoisomerase II inhibitor Calcineurin antagonist K+ channel antagonist Cyclooxygenase inihibitor ACE inhibitor Protein Synthesis inhibitor Cannabinol receptor agonist Nicotinic acetylcholine receptor antagonist Yohimbine Vincristine α2-Adrenoceptor antagonist DNA polymerase inibitor Sildenafil Ampicillin, cyclacillin Neostigmine Etoposide Not yet described* Disopyramide Acetylsalicilic acid Captopril, elanapril Doxycycline Nabilone Vecuronium, pancuronium Idazoxan Vendesine Solvay Pharmaceutical, Dept of intellectual Property and Scientific Information, email: [email protected] Lars Bohlin-University of Uppsala, Division of Pharmacognosy, Dept of Medicinal Chemistry, PO Box 574, 751 23 Uppsala, Sweden. b References Ferris, S. HClinical Therapeutics. 2001, 23, 3. Harvey, A. Drug Discovery Today 2000, 5, 294. Newman, T. J., Cragg, G. M., Sander, K. M. J. Nat. Prods. 2003, 66, 1022; Newman D. J.; Cragg, G. M.; J. Nat. Prod. 2007, 70, 461. Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 Program of the Workshop February 25/2010 8:00 h Registration 8:40 h Open Ceremony Carlos A. Joly (Coordinator - Biota-FAPESP) Vanderlan Bolzani (Chair of the Workshop) Symposium I: Metabolomics and Systems biology as a tool for new drugs discovery 9:00-9:50 Systems Biology: a Gateway to Novel Discoveries Robert Verpoorte (Leiden University – Holland ) 9:50-10:15 Integration of Structure- and Ligands Based Drug Design Approaches for the Discovery of Lead Compounds from Natural Products Adriano Andricopulo (IF-USP, São Carlos-SP) 10:15-10:40 Inhibition of Photophosphorylation and Electron Transport Chain in Thylakoids by Natural Products Maria Fátima das G. Fernandes da Silva (UFSCAR, São Carlos -SP) 10:40-11:05 The Development of New Products from Brazilian Biodiversity Emerson Queiroz (Laboratório Aché, São Paulo, SP) 11:05- 11:20 Coffee break 11:20:12:10h MS-based Metabolomic Approaches Combined with MicroflowNMR Methods for the Search of Original Stress Induced Biomarkers in Plants Jean-Luc Wolfender (Université de Genève) 12:10-12:30 Discussion Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 12:30-14:00 h Lunch Symposium II: Plants and Associate Microorganisms as Potential source of New Biologically Active Molecules 14:00-14:50 Systems Biology of Symbiotic Bacteria and the Search for New Biologically Active Molecules Jon Clardy (Harvard Medical School, USA) 14:50-15:15h Exploring Microbial Interactions in Natural Products Research Monica Talarico Puppo (FCF-USP, Ribeirão Preto, SP) 15:15-15:40h Search for Potential Antitumoral, Antioxidant, Anti-inflammatory, Antifungal, Antidiabetic, Acetylcholinesterase and Myeloperoxidase Inhibitory Natural Compounds from Cerrado and Atlantic Forest Dulce Helena Siqueira Silva (IQ-UNESP, Araraquara, SP) 15:40-16:00h Coffee Break 16:00:16: 25h Footprinting of the ‘Final-fate Compounds’ in Systems Biology: Reading the Nature’s Message Mario Palma (IB-UNESP-Rio Claro, SP) 16:25:16:50h Molecular diversity among basal Angiosperms Massuo Jorge Kato (IQ-USP, São Paulo, SP) 16:50-17:40h Cultured Cyanobacteria: A Promising Source for Novel Bioactive Natural Products Jimmy Orjala (University of Illinois at Chicago, USA) 17:40-18:00 Discussion Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 February 26/2010 Symposium III: New Advance Methodology for the Search Drug Discovery 9:00-9:50 h Arthur Edison (Florida State University - USA) 9:50-9:15h ESI-MS/MS Techniques and Applications for the Analysis of Natural Products Norberto Peporine Lopes (FCF-USP, Ribeirão Preto, SP) 9:15-9:40h Search for highly efficient alcohol dehydrogenases from microorganisms to be applied in enantioselective oxidation of secondary alcohols and bioreduction of ketones Leandro Helgueira Andrade (IQ-USP, São Paulo, SP) 9:40-10:05 Novel application of 2D and 3D-similarity searches to assess compound selectivity among Cytochrome P450 2C9, 2D6 and 3A4 substrates Carlos Alberto Montanari (IQ-USP, São Carlos, SP) 10:05-10:30 Coffee break 10: 30- 11:20h Innovative Strategies to Enhance Structural Diversity of Natural Products and Discovery of their New Uses A. A. Leslie Gunatilaka (The University of Arizona, USA) 11:20- 12:30h Discussion 12:30 h Lunch Symposium IV: New Approach to Screening Biodiversity Source Materials and New Trends in Pharmacology and Toxicology to Select New Targets 14:00-14:50 h Taxol, Tubulin and Tumors: Challenges in the New Era of Cancer Therapeutics Suzan Band Horwitz (Albert Einstein College of Medicine – USA) Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 14:50-15:20h International Workshop on Metabolomics in the Context of Systems Biology: a Rational Approach to Search for Lead Molecules from Nature Newton G. Castro (UFRJ, Rio de Janeiro) 15:20-15:45h Decoding the Signaling Network in Malaria Parasites Célia Regina Silva Garcia (USP, São Paulo, SP) 15: 45-16:10 h Recent Studies of Natural Products Isolated From Brazilian Plants: Evaluation of Antigenotoxicity, Antimutagenicity and Antitumoral Assays Christiane Pienna Soares (Fac. De Farmácia, UNESP – Araraquara, SP) 16:15-16:30 Coffee break 16:30:17:00h Novel Heparinomimetics with Cardiovascular and Inflammatory Disorders Potential Therapeutic Helena B. Nader (Escola Paulista de Medicina, SP) 17:00-17:30 Discussion Close Remarks 17:30-18:00 - Vanderlan da Silva Bolzani (IQ-UNESP, Araraquara, SP) Secretaria do Instituto Virtual da Biodiversidade Programa BIOTA/FAPESP Departamento de Biologia Vegetal – IB/UNICAMP Caixa Posta 6109 – 13093-970 Campinas/SP Fone/Fax (19) 3521 6168 Use in