Natural Product-based Drug Discovery and the Molecular Power House (MPH) Approach

Daniela Barretto Barbosa Trivella
Marjorie Christine Paule Bruder
Fábio Cesar Bonafé Oliveira
Renata Porcaro
Joane Kathelen Rustiguel
Leonardo Bergamasco Ribeiro
Rafael de Felicio
Marcos Guilherme da Cunha
Andrey Fabricio Ziem Nascimento
Ana Carolina Mattos Zeri
Lisandra Ravanelli Pessa
Alessandra Mascarello
Cristiano Ruch Werneck Guimarães
Hatylas Azevedo
Marcia Luana Gomes Perfeito
Eduardo Pagani
Cristina Dislich Ropke

    Daniela Barretto Barbosa Trivella

    Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Laboratório Nacional de Biociências. Rua Giuseppe Maximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP: 13083-970, Campinas, SP, Brasil.

    Coordenadora da Plataforma de Descoberta de Fármacos do Laboratório Nacional de Biociências (LNBio/CNPEM, Campinas, SP). Possui graduação em Ciências Biológicas (2003) e mestrado em Biotecnologia (2006) pela Universidade Federal de Santa Catarina, Doutorado em Ciências Físicas Biomoleculares (2010) pela Universidade de São Paulo, Pós-Doutorado no Instituto de Química, UNICAMP (2010-2013), no Scripps Institute of Oceanography da University of California em San Diego (Estados Unidos, 2012) e no Institute of Cell Signaling da Universidade de Nottingham (Inglaterra, 2015-2016). Seu principal interesse de pesquisa é a descoberta de novos produtos naturais bioativos, moduladores alostéricos de proteínas de interesse farmacêutico e seu desenvolvimento em novos fármacos. Desenvolve novas ferramentas para a descoberta, caracterização e produção de novos produtos naturais e derivados customizados para projetos de descoberta de fármacos com a Academia e a Indústria.

    Marjorie Christine Paule Bruder

    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil

    She holds a degree in Chemistry and Biology from the Université de Metz, a Master's in Biomolecule Engineering from the Université de Montpellier 2 and a PhD in Organic Chemistry from the University of Nottingham. He carried out postdoctoral studies at the University of Campinas (UNICAMP), as well as at the University of Nottingham (UoN, UK) in the context of the Joint Project Program on Drug Discovery CAPES/UoN, in the project "Implementation of a Target-Based Drug Discovery Platform: a CAPES-CNPEM/UNICAMP and Nottingham University Partnership", aiming at training in the area of ​​discovery and development of new drugs. She has experience in the field of Organic Chemistry, with an emphasis on Synthesis of Natural Products, and in Medicinal Chemistry. She is currently coordinator of the Laboratory of Chemistry and Natural Products (LQPN) at the National Biosciences Laboratory (LNBio-CNPEM), where she works in the areas of Chemical Biology and Medicinal Chemistry, and more recently, in the development of chemical tools for applications in bioimaging. .

    Fábio Cesar Bonafé Oliveira

    Centroflora Group - Phytobios. Rua James Clerk Maxwell, 170, Module 2, Techno Park, CEP 13069-380, Campinas, SP, Brazil

    Graduation in Biology, Post-graduation (lato sensu) in Environmental Management. Independent professional in Research Project Management with a focus on flora assets; Rural producer; Independent researcher and collector of Tropical Ornamental Plants with a focus on the Order Zingiberales. It also works in rural development and recovery of degraded areas.

    Renata Porcaro

    Centroflora Group - Phytobios. Rua James Clerk Maxwell, 170, Module 2, Techno Park, CEP 13069-380, Campinas, SP, Brazil

    Joane Kathelen Rustiguel

    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil

    Specialist in materials development at the Laboratory of Chemistry and Natural Products (LQPN) of the National Biosciences Laboratory (LNBio/CNPEM, Campinas-SP). He holds a degree in Biological Physics from the Universidade Estadual Paulista - UNESP "Júlio de Mesquita Filho" (2004-2007), a Master's degree in Science from the Faculty of Pharmaceutical Sciences of Ribeirão Preto - FCFRP-USP (2008-2010) and a PhD in Sciences from the Faculty of Pharmaceutical Sciences of Ribeirão Preto - FCFRP-USP (2010-2014). He carried out a post-doctorate in structural biology with an emphasis on the study of human galectins and animal toxins, with an internship at the University of Zaragoza, working in the field of steady-state enzyme kinetics. He has experience in molecular biology, biochemistry, immunochemistry and structural biology, working mainly in the subareas: cloning and heterologous expression of proteins, macromolecule crystallography, molecular modeling, protein immunodetection and differential scanning fluorimetry.

    Leonardo Bergamasco Ribeiro

    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil

    He holds a degree in Chemistry from the Universidade Estadual Paulista Júlio de Mesquita Filho (2015) and a master's degree in Chemistry from the Universidade Estadual Paulista Júlio de Mesquita Filho (2018). He is currently a technology development analyst at the National Center for Research in Energy and Materials. He has experience in the field of Natural Products Chemistry, with an emphasis on Isolation and identification of secondary metabolites, development of chromatographic methods and validation.

    Rafael de Felicio

    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil

    Graduated in Pharmacy-Biochemistry from the Faculty of Pharmaceutical Sciences of Ribeirão Preto (University of São Paulo), in 2007 and, Master and Doctor in Sciences, from the Postgraduate Program in Pharmaceutical Sciences, area of ​​concentration Natural and Synthetic Products ( Concept 7 Capes), from FCFRP-USP. He carried out a research internship abroad (BEPE-FAPESP), at the Scripps Institution of Oceanography - SIO, University of California San Diego - UCSD (Sep/2012 - Aug/2013) with emphasis on new de-replication methodologies (molecular networking) in application to discovery of new metabolites of marine cyanobacteria. He held a post-doc focusing on the construction and chemical analysis of a library of natural products for drug discovery (2015-2016) at LNBio/CNPEM (Campinas/SP, Brazil) where he is currently Specialist in Technological Development I working mainly in the area of ​​metabolomics of natural products with a focus on drug discovery and the development of platforms for the early discovery of bioactive natural products in complex mixtures.

    Marcos Guilherme da Cunha

    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil

    Graduated in Pharmacy-Biochemistry from the Federal University of Alfenas - Unifal-MG. Master and Doctor in Dentistry - Pharmacology, Anesthesiology and Therapeutics Area (CAPES=7) by the Faculty of Dentistry of Piracicaba/UNICAMP. He held a sandwich doctorate at Molecular Targets Laboratory, National Cancer Institute (NCI/NIH), Frederick, MD, USA from Jun/2013 to Jun/2014. He has experience in the area of isolation and identification of compounds of natural origin and evaluation of their biological activities. He currently works as a Technological Development Specialist at the chemistry and natural products laboratory at LNBio/CNPEM.

    Andrey Fabricio Ziem Nascimento

    National Synchrotron Light Laboratory (LNLS), National Center for Research in Energy and Materials (CNPEM), CEP 13083-100, Campinas, SP, Brazil

    He holds a degree in Pharmacy from the Federal University of Santa Catarina (UFSC) (2009) and a PhD in Functional and Molecular Biology (Biochemistry) from the State University of Campinas (UNICAMP) (2014). She has experience in the fields of Structural Biology, Macromolecule Crystallography, Molecular Biology and Pharmacology. During graduation he worked as a scientific initiation student at the Experimental Pharmacology Laboratory (UFSC) working mainly on the study of signaling pathways involved in pain and inflammation processes. The doctorate was developed at the National Biosciences Laboratory (LNBio - CNPEM) and working in the area of ​​Structural Molecular Biology and Molecular Biophysics with emphasis on macromolecule crystallography, biochemistry and macromolecule spectroscopy, which revealed for the first time the structure of the domain of charge binding of the three human myosin V and worked with new phasing methods. In addition, he completed two-month internships at the Structural Genomics Consortium at the University of Oxford (United Kingdom) and 3 months at the Institut de Biologia Molecular de Barcelona (Spain), in which he worked mainly in large-scale structural studies of unconventional myosins and developments of ab initio phasing methods for medium and low resolution data, respectively. He carried out a postdoctoral degree in structural biology of epigenetic targets of T. cruzi at the Carlos Chagas Institute (FIOCRUZ/PR), at the Institut de Biologia Molecular de Barcelona (Spain), in which he worked in a collaborative project with the ALBA-CELLS synchrotron (Spain) ), with the objective of extending the resolution limits of the ARCIMBOLDO program, which performs ab initio phasing of macromolecules and is capable of solving difficult problems of molecular substitution and in the macromolecular crystallography (MX2) beamline of the National Synchrotron Light Laboratory (LNLS). -CNPEM). He is currently a researcher at the MX2 beamline at the National Synchrotron Light Laboratory, working mainly on the development of new methods of data collection and phasing.

    Ana Carolina Mattos Zeri

    National Synchrotron Light Laboratory (LNLS), National Center for Research in Energy and Materials (CNPEM), CEP 13083-100, Campinas, SP, Brazil

    Graduated in Basic Physics from the Institute of Physics and Chemistry of São Carlos (1994), with a Master's degree in Physics from the Institute of Physics and Chemistry of São Carlos (1997), Master's in Chemistry and Biochemistry - University of Pennsylvania (2000), PhD in Chemistry - University of California, San Diego (2003) and postdoctoral fellow in Biophysics at the University of California, Berkeley (2003-2006). She has experience in the field of Biophysics, with an emphasis on Structural Biology and specialization in Nuclear Magnetic Resonance, X-Ray Crystallography and Optical Forceps. She is currently a researcher at the National Synchrotron Light Laboratory / National Center for Research in Energy and Materials (CNPEM), in Campinas, SP. She is involved in the planning and construction of one of the beamlines and experimental stations for the new electron accelerator, Sirius. The Manaca beamline is dedicated to protein structural studies.

    Lisandra Ravanelli Pessa

    Aché Laboratórios Farmacêuticos, Presidente Dutra-Pista Lateral Highway, s/n, Porto da Igreja, CEP 07034-904, Guarulhos, SP, Brazil

    Bachelor's degree in Biochemical Pharmacy from the University of São Paulo and a Master's student in Scientific and Technological Policy from the Institute of Geosciences of the University of Campinas. She works in Research, Development and Innovation in the pharmaceutical industry, with an emphasis on drug discovery of natural products.

    Alessandra Mascarello

    Aché Laboratórios Farmacêuticos, Presidente Dutra-Pista Lateral Highway, s/n, Porto da Igreja, CEP 07034-904, Guarulhos, SP, Brazil

    Graduated in Chemistry from the Federal University of Santa Catarina - UFSC (2006); Masters (2009) and PhD (2012) from the same institution, with a sandwich doctorate internship at Sapienza Università di Roma and Università degli studi di Siena (2010-2011). She was a CNPq postdoctoral fellow in Medicinal Chemistry at Sapienza Università di Roma (2013-2014) and in the CNPq Young Talents Program at the Center for Molecular and Structural Biology at UFSC (2014-2015). In 2015, she joined the Aché Laboratories team as Research and Innovation Coordinator and is currently Research, Innovation and New Technologies Manager at the same company. She has experience managing teams and new drug projects in the discovery phase. She has >60 publications, including scientific articles, reviews, book chapters and patents.

    Cristiano Ruch Werneck Guimarães

    Aché Laboratórios Farmacêuticos, Presidente Dutra-Pista Lateral Highway, s/n, Porto da Igreja, CEP 07034-904, Guarulhos, SP, Brazil

    He holds a degree in Chemical Engineering from the Federal University of Rio de Janeiro (1996), a Master's degree in Chemistry from the Federal University of Rio de Janeiro (1998), a PhD in Chemistry from the Federal University of Rio de Janeiro (2001) and a Post-Doctorate in Chemistry from the Yale University (2005). She is currently a Scientist at Pfizer, Inc., USA. He has experience in the areas of Organic Chemistry and Physical Chemistry with an emphasis on Medicinal Chemistry, Computational and Physical-Organic Chemistry, working mainly on the following topic: Drug Design.

    Hatylas Azevedo

    Aché Laboratórios Farmacêuticos, Presidente Dutra-Pista Lateral Highway, s/n, Porto da Igreja, CEP 07034-904, Guarulhos, SP, Brazil

    Doctor of Science from the Faculty of Medicine of the University of São Paulo, Master in Biotechnology from the University of São Paulo and Bachelor of Science in Biomedical Sciences from the Federal University of São Paulo. Has experience in the areas of Systems Biology, Genomics, Bioinformatics and Drug Discovery. He is currently Research, Development and Innovation Manager at Aché Laboratórios Farmacêuticos. He is also a Collaborating Researcher and Advisor in the Discipline of Urology at the Federal University of São Paulo.

    Marcia Luana Gomes Perfeito

    Centroflora Group - Phytobios. Rua James Clerk Maxwell, 170, Module 2, Techno Park, CEP 13069-380, Campinas, SP, Brazil

    Biomedical, graduated at the Federal University of Piauí (UFPI), Master in Biotechnology (UFPI) and PhD student in Biotechnology at RENORBIO, with experience in the area of biochemical prospection of molecules for pharmacological use and use of spectroscopic techniques, such as mass spectrometry, HPLC and GC-MS. Specialist in MBA in Auditing in Health Services from the institution Centro Integrado de Post-Graduation, Extension and Research (UNIPOS). Currently, Research and Development Analyst at Centroflora Group, developing research projects in the area of natural products with application to the pharmaceutical industry.

    Eduardo Pagani

    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil

    Physician working for 20 years in pre-clinical and clinical drug development. Former drug development manager at the National Biosciences Laboratory at LNBio/CNPEM and former coordinator of the Human on a Chip Project at LNBio/CNPEM. Graduated in Medicine from USP (1986), specialization in Pharmaceutical Medicine from UNIFESP (1995), Masters in Molecular Biology from UNIFESP (1995), PhD in Sciences from USP (1999) and training in Clinical Research from the Schering Plow Research Institute of New Jersey USA (2002). He is former president of the Brazilian Medical Association of Phytotherapy, former advisor to CONCEA and member of the Technical Chamber of Phytotherapics of ANVISA.

    Cristina Dislich Ropke

    Centroflora Group - Phytobios. Rua James Clerk Maxwell, 170, Module 2, Techno Park, CEP 13069-380, Campinas, SP, Brazil

    Director of Innovation at Centroflora Group and CEO of Phytobios Pesquisa Desenvolvimento e Inovação Ltda, a company of Technological Innovation Based on Biodiversity. Graduation, Master's and Doctorate in Pharmacy-Biochemistry. Fluent German and English. Experience in writing projects for government support and requests for authorization of access to genetic heritage for research, bioprospecting and technological development purposes. Inventor 5 patent applications. Acting in intellectual property and partnership with universities and ICTs. Winner of 6 awards from the Brazilian Association of Cosmetology and 1 award for Best work from the dermatology section of SOT published in Cutaneous and Ocular Toxicology. During her postdoctoral studies, she worked with the evaluation of natural products in the prevention of skin cancer. During this period, she had 2 Scientific Initiation Orientations and 1 PhD co-supervision and created the discipline FBF5780-1-Pharmaceutical strategies for the prevention of skin damage induced by solar radiation: natural antioxidants for the Postgraduate Program at FCF-USP . Tutor of the IEL Inova Talentos Program.Cursos at the MIT Sloan School of Management."Developing and Managing a Successful Technology and Product Strategy"​ and "Fundamentals of Finance for the Technical Executive". Director of Biodiversity at ABIFINA.

Keywords

Drug Discovery and Development
Natural Products
Brazilian Biodiversity
Power House
Crystallography
Metabolomics

Abstract

Natural product-based drug discovery is experiencing a new era thanks to the use of cutting-edge technologies and integrated approaches to overcome the difficulties inherent to natural products research. These are highly complex and innovative chemical substances produced by the biota, in particular sessile organisms such as plants and microorganisms, and represent the main source of inspiration for new drugs. The increasing interest in the discovery of medicines based on natural products has pushed the development of new approaches for the identification, characterization and resupply of natural products, which can address some of the challenges related to the development of drugs inspired by molecules from the biodiversity. The aim is to detect and characterize new bioactive natural products, at the same time as reducing costs and time to obtain these molecules. For this, it is necessary to innovate in the processes and technologies applied to the discovery of drugs from natural products. The Molecular Power House (MPH) approach presented in this work makes use of integrated technologies as a way to overcome classic bottlenecks in plant natural products research, which aligned with access to the greatest biodiversity on the planet, positions Brazil in the global scenario of discovering innovative drugs.

References

  1. Newman DJ, Cragg GM. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod. 2020; 83: 770-803. [CrossRef] [PubMed].
  2. Cremosnik GS, Liu J, Waldmann H. Guided by evolution: from biology oriented synthesis to pseudo natural products. Nat Prod Rep. 2020; 37: 1497-1510. [CrossRef] [PubMed].
  3. Bruder M, Polo G, Trivella DBB. Natural allosteric modulators and their biological targets: molecular signatures and mechanisms. Nat Prod Rep. 2020: 37. [CrossRef] [PubMed].
  4. Allard PM, Péresse T, Bisson J, Gindro K, Marcourt L, Pham VC et al. Integration of molecular networking and in-silico MS/MS fragmentation for natural products dereplication. Anal Chem. 2016; 88: 3317-3323. [CrossRef] [PubMed].
  5. Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018; 46: D1074-D1082. [CrossRef] [PubMed].
  6. Lu S, He X, Ni D, Zhang J. Allosteric modulator discovery: from serendipity to structure-based design. J Med Chem. 2019; 62: 6405-6421. [CrossRef] [PubMed].
  7. Flemming A. Allosteric phosphatase inhibitor puts brake on cancer cells. Nat Rev Drug Discov. 2016; 15: 530-531. [Link].
  8. Drag M, Salvesen GS. Emerging principles in protease-based drug discovery. Nat Rev Drug Discov. 2010; 9: 690-701. [CrossRef] [PubMed].
  9. Ni D, Lu S, Zhang J. Emerging roles of allosteric modulators in the regulation of protein-protein interactions (PPIs): a new paradigm for PPI drug discovery. Med Res Rev. 2019; 39: 2314-2342. [CrossRef] [PubMed].
  10. Coughlin Q, Hopper AT, Blanco M-J, Tirunagaru V, Robichaud AJ, Doller D. Allosteric modalities for membrane-bound receptors: insights from drug hunting for brain diseases. J Med Chem. 2019; 62: 5979-6002. [CrossRef] [PubMed].
  11. Liu X, Lu S, Song K, Shen Q, Ni D, Li Q et al. Unraveling allosteric landscapes of allosterome with ASD. Nucleic Acids Res. 2020; 48: D394-D401. [CrossRef] [PubMed].
  12. Nussinov R, Tsai CJ. Allostery in disease and in drug discovery. Cell. 2013; 153: 293-305. [CrossRef] [PubMed].
  13. Mushtaq S, Abbasi BH, Uzair B, Abbasi R. Natural products as reservoirs of novel therapeutic agents. EXCLI J. 2018; 17: 420-451. [CrossRef] [PubMed].
  14. Wouters OJ, McKee M, Luyten J. Estimated research and development investment needed to bring a new medicine to market, 2009-2018. JAMA. 2020; 323: 844. [CrossRef] [PubMed].
  15. Thornburg CC, Britt JR, Evans JR, Akee RK, Whitt JA, Trinh SK et al. NCI Program for natural product discovery: a publicly-accessible library of natural product fractions for high-throughput screening. ACS Chem Biol. 2018; 13: 2484-2497. [CrossRef] [PubMed].
  16. de Felício R, Ballone P, Bazzano CF, Alves LFG, Sigrist R, Infante GP et al. Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions. Metabolites. 2021; 11: 107. [CrossRef] [PubMed].
  17. Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y et al. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat Biotechnol. 2016; 34: 828-837. [CrossRef] [PubMed].
  18. Trivella DBB, De Felicio R. The tripod for bacterial natural product discovery: Genome mining, silent pathway induction, and mass spectrometry-based molecular networking. mSystems. 2018: 3. [CrossRef] [PubMed].
  19. Aché Laboratories. Report 2020. 2020. [Link]
  20. Brasil. Ministério do Planejamento, Orçamento e Gestão – MPOG. Instituto Brasileiro de Geografia e Estatística - IBGE. Produção da extração vegetal e da silvicultura. 2014; 29:1-56. ISBN 0103-8435. [Link].
  21. Grabher C. A governança e a sustentabilidade do extrativismo do jaborandi na Amazônia e transição para o Cerrado e a Caatinga. Porto Alegre. 2015. Dissertação de Mestrado. [Programa de Pós-Graduação em Desenvolvimento Rural] - Faculdade de Ciências Econômicas. Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre. 2015. [Link].
  22. Caldeira CF, Giannini TC, Ramos SJ, Vasconcelos S, Mitre SK, Pires JP et al. Sustainability of Jaborandi in the eastern Brazilian Amazon. Perspect. Perspect Ecol Conserv. 2017; 15: 161-171. [CrossRef].

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Author(s)

  • Daniela Barretto Barbosa Trivella
    Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Laboratório Nacional de Biociências. Rua Giuseppe Maximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP: 13083-970, Campinas, SP, Brasil.
  • Marjorie Christine Paule Bruder
    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil
  • Fábio Cesar Bonafé Oliveira
    Centroflora Group - Phytobios. Rua James Clerk Maxwell, 170, Module 2, Techno Park, CEP 13069-380, Campinas, SP, Brazil
  • Renata Porcaro
    Centroflora Group - Phytobios. Rua James Clerk Maxwell, 170, Module 2, Techno Park, CEP 13069-380, Campinas, SP, Brazil
  • Joane Kathelen Rustiguel
    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil
  • Leonardo Bergamasco Ribeiro
    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil
  • Rafael de Felicio
    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil
  • Marcos Guilherme da Cunha
    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil
  • Andrey Fabricio Ziem Nascimento
    National Synchrotron Light Laboratory (LNLS), National Center for Research in Energy and Materials (CNPEM), CEP 13083-100, Campinas, SP, Brazil
  • Ana Carolina Mattos Zeri
    National Synchrotron Light Laboratory (LNLS), National Center for Research in Energy and Materials (CNPEM), CEP 13083-100, Campinas, SP, Brazil
  • Lisandra Ravanelli Pessa
    Aché Laboratórios Farmacêuticos, Presidente Dutra-Pista Lateral Highway, s/n, Porto da Igreja, CEP 07034-904, Guarulhos, SP, Brazil
  • Alessandra Mascarello
    Aché Laboratórios Farmacêuticos, Presidente Dutra-Pista Lateral Highway, s/n, Porto da Igreja, CEP 07034-904, Guarulhos, SP, Brazil
  • Cristiano Ruch Werneck Guimarães
    Aché Laboratórios Farmacêuticos, Presidente Dutra-Pista Lateral Highway, s/n, Porto da Igreja, CEP 07034-904, Guarulhos, SP, Brazil
  • Hatylas Azevedo
    Aché Laboratórios Farmacêuticos, Presidente Dutra-Pista Lateral Highway, s/n, Porto da Igreja, CEP 07034-904, Guarulhos, SP, Brazil
  • Marcia Luana Gomes Perfeito
    Centroflora Group - Phytobios. Rua James Clerk Maxwell, 170, Module 2, Techno Park, CEP 13069-380, Campinas, SP, Brazil
  • Eduardo Pagani
    National Center for Research in Energy and Materials (CNPEM), National Biosciences Laboratory. Rua Giuseppe Máximo Scolfaro, 10000, Guara, Polo II de Alta Tecnologia, CEP 13083-970, Campinas, SP, Brazil
  • Cristina Dislich Ropke
    Centroflora Group - Phytobios. Rua James Clerk Maxwell, 170, Module 2, Techno Park, CEP 13069-380, Campinas, SP, Brazil

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Natural Product-based Drug Discovery and the Molecular Power House (MPH) Approach. Rev Fitos [Internet]. 2022 Mar. 4 [cited 2024 Nov. 22];16(Supl. 2):176-92. Available from: https://revistafitos.far.fiocruz.br/index.php/revista-fitos/article/view/1346
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