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Discovery and development of potential chemotherapeutic agents based on marine invertebrates and associated micro-organisms

Grant number: 05/60175-2
Support type:BIOTA-FAPESP Program - Thematic Grants
Duration: November 01, 2006 - November 30, 2010
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Roberto Gomes de Souza Berlinck
Grantee:Roberto Gomes de Souza Berlinck
Home Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Co-Principal Investigators:Lara Durães Sette
Associated scholarship(s):10/05100-5 - Investigation of biosynthetic routes of polyketides and alkaloids from marine microorganisms, BP.PD
09/02250-9 - Bromotyrosine derivatives from sponge Aiolochroia crassa, BP.MS
08/08053-8 - Chemical and microbiological studies of fungi associated to the marine sponge Dragmacidon reticulata, aiming the production of bioactive secondary metabolites, BP.MS
08/02791-7 - Isolation and screening of fungi associated to the ascidian Didemnum sp. capable to produce secondary metabolites of pharmacological importance, BP.IC

Abstract

Marine natural products isolated from both marine invertebrates and microorganisms have received increased attention during the last 5 O years due to their structural complexity and biological activities. ln particular marine sponges, ascidians, octocorals, bryozoans, as well as marine fungi and bacteria, have shown to be prolific sources of potent1y active and stmcturally unique secondary metabolites. Although Brazil has a 8.000 km long coastline, the knowledge of marine natural products from Brazilian marine organisms is still limited. The proposal of this project is the chemical investigation of biologically active crude extracts obtained from marine invertebrates and marine microorganisms collected in different regions of the Brazilian coastline. Extracts of marine invertebrates active already tested in assays of cytotoxic and antituberculosis activities, as well as of antimicrobial activity against both antibiotic-sensitive and antibiotic-resistant human pathogenic microbes and of inhibition of specific enzymes implied in the life cycle of pathogenic protozoa, will be subjected to dereplication by LC-PDA-MS before a chromatographic fractionation toward the isolation of biologically active compO1unds. In parallel, marine fungi and bacteria isolated from marine invertebrates (sponge and ascidians) will be grown in optimized artificial media in order to produce secondary metabolites. The marine microbe growth media will be extracted by adsorption on polymeric resin and by liquid-liquid extraction. Extracts from marine microbes will be subjected to the same above mentioned bioassays. Additionally, a new set of bioassays related to the inhibition or stimulation of chemical mediators implied in immunomodulation processes will be applied to the whole crude extract collection (> 500), in order to search for active extracts. Active extracts will be subjected to a dereplication by LC-PDA MS analysis, in order to get information about crude extracts chemical profiles and prioritize the isolation of novel bioactive compounds. After dereplication, marine microbial extracts will also be subjected to fractionation aiming the isolation of pure active metabolites. Pure chemical entitites obtained from marine invertebrates and microorganisms will be spectroscopically identified and evaluated in the bioassays in which the original crude extract was active, aiming to obtain information on their mechanism of action. (AU)

Articles published in Agência FAPESP about the research grant
Researchers describe five new species of marine invertebrates 

Scientific publications (20)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE CASTRO, MARCOS V.; IOCA, LAURA P.; WILLIAMS, DAVID E.; COSTA, BRUNA Z.; MIZUNO, CAROLINA M.; SANTOS, MARIO F. C.; DE JESUS, KAREN; FERREIRA, EVERTON L. F.; SELEGHIM, MIRNA H. R.; SETTE, LARA D.; PEREIRA FILHO, EDENIR R.; FERREIRA, ANTONIO G.; GONCALVES, NATALIA S.; SANTOS, RAQUEL A.; PATRICK, BRIAN O.; ANDERSEN, RAYMOND J.; BERLINCK, ROBERTO G. S. Condensation of Macrocyclic Polyketides Produced by Penicillium sp DRF2 with Mercaptopyruvate Represents a New Fungal Detoxification Pathway. Journal of Natural Products, v. 79, n. 6, p. 1668-1678, JUN 2016. Web of Science Citations: 11.
LIMA, BRUNA DE A.; DE LIRA, SIMONE P.; KOSSUGA, MIRIAM H.; GONCALVES, REGINALDO B.; BERLINCK, ROBERTO G. S.; KAMIYA, REGIANNE U. Halistanol sulfate A and rodriguesines A and B are antimicrobial and antibiofilm agents against the cariogenic bacterium Streptococcus mutans. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 24, n. 6, p. 651-659, NOV-DEC 2014. Web of Science Citations: 6.
BONUGLI-SANTOS, RAFAELLA C.; DURRANT, LUCIA REGINA; SETTE, LARA DURAES. The Production of Ligninolytic Enzymes by Marine-Derived Basidiomycetes and Their Biotechnological Potential in the Biodegradation of Recalcitrant Pollutants and the Treatment of Textile Effluents. WATER AIR AND SOIL POLLUTION, v. 223, n. 5, p. 2333-2345, JUN 2012. Web of Science Citations: 19.
KOSSUGA, MIRIAM H.; ROMMINGER, STELAMAR; XAVIER, CAMILA; MILANETTO, MARILIA C.; DO VALLE, MILENE Z.; PIMENTA, ELI F.; MORAIS, RAQUEL P.; DE CARVALHO, ERICA; MIZUNO, CAROLINA M.; CORADELLO, LUIS FERNANDO C.; BARROSO, VINICIUS DE M.; VACONDIO, BRUNA; JAVAROTI, DARCI C. D.; SELEGHIM, MIRNA H. R.; CAVALCANTI, BRUNO C.; PESSOA, CLAUDIA; MORAES, MANOEL O.; LIMA, BRUNA A.; GONCALVES, REGINALDO; BONUGLI-SANTOS, RAFAELLA C.; SETTE, LARA D.; BERLINCK, ROBERTO G. S. Evaluating methods for the isolation of marine-derived fungal strains and production of bioactive secondary metabolites. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 22, n. 2, p. 257-267, MAR-APR 2012. Web of Science Citations: 27.
FÁBIO R. PEREIRA; ROBERTO G. S. BERLINCK; EDSON RODRIGUES FILHO; KATYUSCYA VELOSO; ANTONIO G. FERREIRA; VINICIUS PADULA. Metabólitos secundários dos nudibrânquios Tambja stegosauriformis, Hypselodoris lajensis e Okenia zoobotryon e dos briozoários Zoobotryon verticillatum e Bugula dentata da costa do Brasil. Química Nova, v. 35, n. 11, p. -, 2012.
MARTINS, MARIANA PROVEDEL; MOUAD, ANA MARIA; BOSCHINI, LETICIA; REGALI SELEGHIM, MIRNA HELENA; SETTE, LARA DURAES; MELEIRO PORTO, ANDRE LUIZ. Marine Fungi Aspergillus sydowii and Trichoderma sp Catalyze the Hydrolysis of Benzyl Glycidyl Ether. MARINE BIOTECHNOLOGY, v. 13, n. 2, p. 314-320, APR 2011. Web of Science Citations: 23.
TEMPONE, ANDRE G.; DE OLIVEIRA, CAMILA MARTINS; BERLINCK, ROBERTO G. S. Current Approaches to Discover Marine Antileishmanial Natural Products. Planta Medica, v. 77, n. 6, p. 572-585, APR 2011. Web of Science Citations: 66.
MAYER, ALEJANDRO M. S.; RODRIGUEZ, ABIMAEL D.; BERLINCK, ROBERTO G. S.; FUSETANI, NOBUHIRO. Marine pharmacology in 2007-8: Marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous system, and other miscellaneous mechanisms of action. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 153, n. 2, p. 191-222, MAR 2011. Web of Science Citations: 151.
DA SILVA, FERNANDA R.; TESSIS, ANA CLAUDIA; FERREIRA, PATRICIA F.; RANGEL, LUCIANA P.; GARCIA-GOMES, ALINE S.; PEREIRA, FABIO R.; BERLINCK, ROBERTO G. S.; MURICY, GUILHERME; FERREIRA-PEREIRA, ANTONIO. Oroidin Inhibits the Activity of the Multidrug Resistance Target Pdr5p from Yeast Plasma Membranes. Journal of Natural Products, v. 74, n. 2, p. 279-282, FEB 2011. Web of Science Citations: 13.
PIMENTA, ELI F.; VITA-MARQUES, ALINE M.; TININIS, ARISTEU; SELEGHIM, MIRNA H. R.; SETTE, LARA D.; VELOSO, KATYUSCYA; FERREIRA, ANTONIO G.; WILLIAMS, DAVID E.; PATRICK, BRIAN O.; DALISAY, DORALYN S.; ANDERSEN, RAYMOND J.; BERLINCK, ROBERTO G. S. Use of Experimental Design for the Optimization of the Production of New Secondary Metabolites by Two Penicillium Species. Journal of Natural Products, v. 73, n. 11, p. 1821-1832, NOV 2010. Web of Science Citations: 32.
BONUGLI-SANTOS, RAFAELLA C.; DURRANT, LUCIA R.; SETTE, LARA D. Laccase activity and putative laccase genes in marine-derived basidiomycetes. FUNGAL BIOLOGY, v. 114, n. 10, p. 863-872, OCT 2010. Web of Science Citations: 21.
MENEZES, CLAUDIA B. A.; BONUGLI-SANTOS, RAFAELLA C.; MIQUELETTO, PAULA B.; PASSARINI, MICHEL R. Z.; SILVA, CARLOS H. D.; JUSTO, MARIANA R.; LEAL, REBECA R.; FANTINATTI-GARBOGGINI, FABIANA; OLIVEIRA, VALERIA M.; BERLINCK, ROBERTO G. S.; SETTE, LARA D. Microbial diversity associated with algae, ascidians and sponges from the north coast of Sao Paulo state, Brazil. MICROBIOLOGICAL RESEARCH, v. 165, n. 6, p. 466-482, 2010. Web of Science Citations: 86.
MORAIS, RAQUEL P.; LIRA, SIMONE P.; SELEGHIM, MIRNA H. R.; BERLINCK, ROBERTO G. S. A Method for Dextruxin Analysis by HPLC-PDA-ELSD-MS. Journal of the Brazilian Chemical Society, v. 21, n. 12, p. 2262-2271, 2010. Web of Science Citations: 9.
RENATA C. GANDOLFI; MARINA B. MEDINA; ROBERTO G. S. BERLINCK; SIMONE P. LIRA; FABIO CÍCERO DE SÁ GALETTI; CÉLIO L. SILVA; KATYUSCYA VELOSO; ANTONIO G. FERREIRA; EDUARDO HAJDU; SOLANGE PEIXINHO. Metabólitos secundários das esponjas Aplysina fistularis e Dysidea sp. e atividade antituberculose da 11-cetofistularina-3. Química Nova, v. 33, n. 9, p. 1853-1858, 2010.
SILVA, MICHELLI M.; BERGAMASCO, JULIANA; LIRA, SIMONE P.; LOPES, NORBERTO P.; HAJDU, EDUARDO; PEIXINHO, SOLANGE; BERLINCK, ROBERTO G. S. Dereplication of Bromotyrosine-derived Metabolites by LC-PDA-MS and Analysis of the Chemical Profile of 14 Aplysina Sponge Specimens from the Brazilian Coastline. AUSTRALIAN JOURNAL OF CHEMISTRY, v. 63, n. 6, p. 886-894, 2010. Web of Science Citations: 10.
ROCHA, LENILSON C.; FERREIRA, HERCULES V.; PIMENTA, ELI F.; BERLINCK, ROBERTO G. S.; SELEGHIM, MIRNA H. R.; JAVAROTI, DARCI C. D.; SETTE, LARA D.; BONUGLI, RAFAELLA C.; PORTO, ANDRE L. M. Bioreduction of alpha-chloroacetophenone by whole cells of marine fungi. Biotechnology Letters, v. 31, n. 10, p. 1559-1563, OCT 2009. Web of Science Citations: 29.
WILLIAMS, DAVID E.; MARQUES, SUZI O.; HAJDU, EDUARDO; PEIXINHO, SOLANGE; ANDERSEN, RAYMOND J.; BERLINCK, ROBERTO G. S. Pyrodysinoic Acid Derivatives from the Marine Sponge Dysidea robusta. Journal of Natural Products, v. 72, n. 9, p. 1691-1694, SEP 2009. Web of Science Citations: 9.
ROSANA M. DA ROCHA; NADIA Y. K. BONNET. Ascídias (Tunicata, Ascidiacea) introduzidas no Arquipélago de Alcatrazes, São Paulo. IHERINGIA SERIE ZOOLOGIA, v. 99, n. 1, p. 27-35, Mar. 2009.
KOSSUGA, MIRIAM H.; LIRA, SIMONE P.; MCHUGH, SHAYNA; TORRES, YOHANDRA R.; LIMA, BRUNA A.; GONCALVES, REGINALDO; VELOSO, KATYUSCYA; FERREIRA, ANTONIO G.; ROCHA, ROSANA M.; BERLINCK, ROBERTO G. S. Antibacterial Modified Diketopiperazines from two Ascidians of the Genus Didemnum. Journal of the Brazilian Chemical Society, v. 20, n. 4, p. 704+, 2009. Web of Science Citations: 11.
REIMAO, JULIANA QUERO; MIGOTTO, ALVARO ESTEVES; KOSSUGA, MIRIAM H.; BERLINCK, ROBERTO G. S.; TEMPONE, ANDRE GUSTAVO. Antiprotozoan activity of Brazilian marine cnidarian extracts and of a modified steroid from the octocoral Carijoa riisei. Parasitology Research, v. 103, n. 6, p. 1445-1450, NOV 2008. Web of Science Citations: 26.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
Filed patent(s) as a result of this research project

PROCESSO DE OBTENÇÃO DA ENZIMA LACASE POR FUNGO MARINHO, ENZIMA LACASE E USO DA MESMA BR1020140085025 - Universidade Estadual de Campinas (UNICAMP) ; Universidade Estadual Paulista (UNESP) . Lara Durães Sette; Rafaella Costa Bonugli Santos; Cárol Cabral Terrone; Eleonora Cano Carmona - April 2014, 09