Challenges and Possibilities onthe Development of Biodiversity-
Derived Products in BrazilLeticia Veras Costa Lotufo
Departamento de Farmacologia
ICB-USP
Biobased Economy WorkshopApril, 06th, 2017
INCTBioNat
Industries from Biodiversity
Pharmaceuticals
EthnobotanicalsPhytomedicines
Cosmeticals Personal care
Biological Control
Crop protectionBiomimetics
Biomonitoring
Bioremediation
Horticulture
Agriculture
Biofuels
Ecotourism
Restoration
Brazil holds one of the greatest diversity in the whole planet!
A very sophisticated synthetic lab!
GeneticDiversity
GeneticDiversity
BiologicalDiversity
GeneticDiversity
BiologicalDiversity
ChemicalDiversity
Monroe Wall e Mansukh Wani - Triangle Institute-USA
Taxol® isolated from Taxus brevifolia
• bioprospection of 147.000 species
• First collect of plant material -1962
• Phytochemistry publication -1971
• Clinical trials started in 1983
• Commercialized by Bristol-Myers
Squibb in 1994
•Sales: ~US$142 millions 2011
•Holton’s four-step synthesis
Senter & Sievers, 2012. Nature Biotechnology, 30, 631.
Exenatide (INN, marketed as Byetta) isone of a new class of medications(incretin mimetics) approved by FDA(Apr 2005) for the treatment of diabetesmellitus type 2)
The Gila Monster and the development of Byetta®
Heloderma suspectum (Helodermatidae)39-amino-acid peptide
D. Drucker, J. Buse, K. Taylor, D. Kendall, M. Trautmann, D. Zhuang, L. Porter. The Lancet, 372, 2008, 1240-1250
10
Ronald Quinn, et al. Nature Reviews, 2015
FANTASTIC BRAZILIAN BIODIVERSITY
Simon M F et al. PNAS
2009;106:20359-20364
✓ Brazil is a country with a unique terrestrial biodiversity……..✓ 70% of all species, including animals and plants on Earth;✓ 15-20% of the World’s biodiversity – huge endemism;✓ ~ 7% of the total terrestrial plant species are endemics✓ ~ 18.000 species occur on in Brazilian territory(Lewinsonhn,T. M. 2002)
Amazonian
“Cerrado”
Pantanal (Wetland)
Caatinga
Atlantic Forest
Subtropical Grassland
A wonderful place for the development
of natural products chemistry research
2005 – The first antiinflammatory herbal
medicine completely developed in Brazil
Fruit from the amazonian palmtreeEuterpe oleraceaArecaceae Family
AÇAÍ BIOECONOMY
15% PULP
+85% SEEDS
- Ice Cream- Jam- Liquor- Chocolates
Main uses:- FERTILIZERS- CURTUME / TANINO- XAXINS - INSULATORS
USES WITH GREATER VALUE ADDED - INDUSTRY
APPLICATIONS - AUTOMOBILISTIS- DRUGS
Low value
Prospecting of secondary metabolites of various classes and
biopolymers
Frequency of patent applications deposited in the period between 2003 and 2008, coming from the State of Amazonas, executed by their respective industrial sector.
Frickmann, et al. J. Technol. Manag. Innov., 6 (4) 2011
Distribution of research groups involved with medicinal plants, phytotherapic and phytocosmetic by Brazilian Amazonia, per category of STI, in 2010
11 JUNE 2010 VOL 328, SCIENCE www.sciencemag.org
BIOprospecTA“Conservation and Sustainable Use of the Diversity from
Cerrado and Atlantic forest: Chemical Diversity and Prospecting
for Potential Drugs” Coordinator - Vanderlan da Silva Bolzani
Summary of Biodiscovery Project Biota-FAPESP
accomplished at NuBBE in 15th years
Number of field trips: 25 (11 Cerrado e 14 Atlantic Forest)
Total of samples: 1700 extracts from 1100 plants; 150 from
endophytic fungi
Samples identified :
1100 species,
+ 948 genera,
+ 109 family and
~ 102 not identified.
Number of species identified: 346.
Number of species sampled bioassayed : 709 species
Number of Compounds: 634
Bolzani, et. al. Plant Diversity from Brazilian Cerrado and Atlantic Forest as a Tool for Prospecting Potential Therapeutic Drugs. In: Mander, L., Lui, H.-W.(Org.); Verpoorte Ed. COMPREHENSIVE NATURAL PRODUCTS II CHEMISTRY AND BIOLOGY. 133 ed. Oxoford: Elsevier, 2010, v. 3, p. 95
Quite good collection of Natural Products from Brazilian
biodiversity could inspiring some organizational efforts
to attend the main objective of Biota-FAPESP
*****REGULATORY ISSUES – PROBLEMS FOR THE DEVELOPMENT OF SCIENCE AND TECNOLOGY WITH ORGANISMOS FROM OUR BIODIVERSITY
NuBBE Database: Available data
Natural Compounds
Source,References
Chemical properties
Chemical structures In mol2 and SMILES format
Biological properties (experimental)
Molecular weight
molecular volume
cLogP
H-bond acceptors
H-bond donnors
TPSARotablebonds
Violation of Lipinski's rule
Analytical data (HPLC, MS, NMR) under development
Valli, M; et al. J. Nat. Prod. 2013, 76, (3), pp 439–444TPSA: topological polar surface areacLogP: calculated partition coefficient
20Valli, M; et al. J. Nat. Prod. 2013, 76, (3), pp 439–444
http://nubbe.iq.unesp.br/nubbeDB.html
170 Papers
NuBBE Database
640 Compounds
http://nubbe.iq.unesp.br/nubbeDB.html
Dereplication
Medicinal
Chemistry
Virtual
Screening
Metabolomics
NuBBEDB was recently incorporated to ChemSpider-RSC, afree chemical structure database providing fast access to over28 million structures, properties and associated information)
http://www.chemspider.com/Search.aspx?dsn=NuBBE+database
Ronald Quinn, et al. Nature Reviews, 2015
CENTER FOR INNOVATION IN BIODIVERSITY & DRUG DISCOVERY
São Carlos
Headquarter
IFSC-USP
Ribeirão
PretoFCFRP-USP
Araraqu
araIQ-UNESP
CampinasIQ-UNICAMP
São CarlosDQ-UFSCar
Director Coordinator of Technology Transfer
Coordinator of Science Dissemination
Vice-Director
National Institute of Science and Technology on Biodiversity and Natural Products
INCTBioNat
18 Institutions55 PhD Researchers178 Students
Dr. Vanderlan BolzaniCoordinator
UNESP
Dr. Edilberto SilveiraVice-Coordinator
UFC
BRAZIL
EconomicExclusive Zone
Continental Shelf
Amazonian
Pantanal (Wetland)
Subtropical Grassland
“Cerrado”
Caatinga
Atlantic Forest
Biomes
ASPSPRocas Atol
Eudistoma vannamei
Streptromyces sp.
Palythoa variabilis
Actinomadura sp.
Streptromyces sp.
INCTBioNat - Strategies
Discovery of Hits
Marine Organisms Plants Microorganisms
Extracts/ Fractions
Natural Products
Pharmacology/ Toxicology
Bioassays
Hits
ChemosystematicsEthnobotanics
Chemical ecologyGreen chemistry Analytical methods
Chemical documentationMetabolomicsDerreplication
Bioguided fractionationStructure elucidation
Biosynthetic studiesBiocatalysis
SynthesisMedChem
Ecological studiesScale-up production
OSMAC approachBiotransformationBiosynthesisMetagenomics
AntimicrobialAnti parasiticAnticancerAnti-inflamatoryAntioxidantEnzymatic assays
Experimental strategies for sustainable prospection of Brazilian biodiversity
Capa
Inserir imagem escaneada da capa do livro
Maria das Graças Lins Brandão Museu de História Natural e Jardim Botânico
Universidade Federal de Minas Gerais
Challenges:
• Access and Benefits Sharing of Genetic Resources and
Associated Traditional Knowledge - Law No. 13.123 of May 20,
2015
• Intellectual property
• Technology transfer - Interactions with Pharmaceutical
industry
• Science Funding
Acknowledgements
THANK YOU FOR YOUR ATTENTION!!!
