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New secondary metabolites of endophytic and marine organisms as proteasome inhibitors: a validated target against cancer

Grant number: 17/06014-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): June 01, 2017
Effective date (End): July 31, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Roberto Gomes de Souza Berlinck
Grantee:Juliana Regina Gubiani
Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil


The present project aims at the discovery of proteasome inhibitors. The proteasome is the main non-lysosomal proteolytic complex, and is already a validated target for the treatment of multiple myeloma, with potential validation for other human diseases, such as in the treatment of Chagas disease, leishmaniasis and inflammatory diseases. Thus, finding substances capable of inhibiting the proteasome is a validated strategy for multiple myeloma and other neoplasms. In this context, seventeen extracts of fungal and marine origin, among hundreds of extracts tested, presented proteasome inhibitory activity. These extracts will be prioritized for HPLC-UV-MS and UPLC-QTOF analyzes and for bioguided isolation of new proteasome inhibitors. In this way, the objective is to isolate and identify proteasome inhibitors from these extracts from invertebrates and marine and endophytic microorganisms, with unprecedented structural characteristics. (AU)

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Scientific publications (12)
(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)
CHAPLA, VANESSA M.; HONORIO, ALANA E.; GUBIANI, JULIANA R.; VILELA, ADRIANA F. L.; YOUNG, MARIA C. M.; CARDOSO, CARMEN L.; PAVAN, FERNANDO R.; CICARELLI, REGINA M.; PINHEIRO FERREIRA, PAULO MICHEL; BOLZANI, VANDERLAN DA S.; et al. Acetylcholinesterase inhibition and antifungal activity of cyclohexanoids from the endophytic fungus Saccharicola sp.. PHYTOCHEMISTRY LETTERS, v. 39, p. 116-123, . (13/07600-3, 17/06014-4)
KURODA, YUSUKE; NICACIO, KAREN J.; DA SILVA-, JR., ILDEFONSO ALVES; LEGER, PAUL R.; CHANG, STANLEY; GUBIANI, JULIANA R.; DEFLON, VICTOR M.; NAGASHIMA, NOZOMU; RODE, ALEXANDER; BLACKFORD, KATHERINE; et al. Isolation, synthesis and bioactivity studies of phomactin terpenoids. NATURE CHEMISTRY, v. 10, n. 9, p. 938-945, . (13/50228-8, 15/01017-0, 17/06014-4)
RODRIGUEZ, JULIE P. G.; BERNARDI, DARLON I.; GUBIANI, JULIANA R.; DE OLIVEIRA, JULIANA MAGALHAES; MORAIS-URANO, RAQUEL P.; BERTONHA, ARIANE F.; BANDEIRA, KARIN F.; BULLA, JAIRO I. Q.; SETTE, LARA D.; FERREIRA, ANTONIO G.; et al. Water-Soluble Glutamic Acid Derivatives Produced in Culture by Penicillium solitum IS1-A from King George Island, Maritime Antarctica. Journal of Natural Products, v. 83, n. 1, p. 55-65, . (13/23153-7, 16/21341-9, 17/06014-4, 13/50228-8, 16/16033-3)
BERLINCK, ROBERTO G. S.; CRNKOVIC, CAMILA M.; GUBIANI, JULIANA R.; BERNARDI, DARLON I.; IOCA, LAURA P.; QUINTANA-BULLA, JAIRO I.. The isolation of water-soluble natural products - challenges, strategies and perspectives. NATURAL PRODUCT REPORTS, . (13/50228-8, 16/16033-3, 19/00447-1, 20/11691-8, 16/05133-7, 17/06014-4, 16/21341-9, 18/10742-8)
TONON, LUCIANE A. CHIMETTO; RUA, CINTIA; CRNKOVIC, CAMILA M.; BERNARDI, I, DARLON; JUNIOR, OSMINDO R. PIRES; HADDAD, CELIO F. B.; PEDROSA, CAROLINADA S. G.; SOUZA, LETICIA R. Q.; REHEN, STEVENS K.; DE AZEVEDO, GUSTAVO P. R.; et al. Microbiome associated with the tetrodotoxin-bearing anuran Brachycephalus pitanga. Toxicon, v. 203, p. 139-146, . (13/50741-7, 16/14375-4, 16/05133-7, 17/06014-4, 13/50228-8, 16/21341-9, 19/00447-1)
SOUZA, JESSICA A. DE M.; GUBIANI, JULIANA R.; DE SIQUEIRA, KATIA A.; DE CAMARGO, MARIA J.; GARCEZ, WALMIR S.; DE SOUSA, PAULO T.; SOARES, MARCOS A.; ARAUJO, ANGELA R.; NUNES, EMANUEL V. DOS S.; VIEIRA, LUCAS C. C.; et al. Antimicrobial metabolites produced by endophytic fungi associated with the leaves of Vochysia divergens. NATURAL PRODUCT RESEARCH, v. N/A, p. 8-pg., . (17/06014-4, 14/50926-0)
DA SILVA, THALITA FERREIRA; CAVALCANTE, RODRIGO PEREIRA; GUELFI, DIEGO ROBERTO VIEIRA; DE OLIVEIRA, SILVIO CESAR; CASAGRANDE, GLEISON ANTONIO; CAIRES, ANDERSON RODRIGUES LIM; DE OLIVEIRA, FELIPE FERNANDES; GUBIANI, JULIANA REGINA; CARDOSO, JULIANO CARVALHO; MACHULEK JR, AMILCAR. Photo-anodes based on B-doped TiO2 for photoelectrocatalytic degradation of propyphenazone: Identification of intermediates, and acute toxicity evaluation. JOURNAL OF ENVIRONMENTAL CHEMICAL ENGINEERING, v. 10, n. 2, p. 15-pg., . (20/15230-5, 17/06014-4, 19/26210-8)
BANZATO, THAIS P.; GUBIANI, JULIANA R.; BERNARDI, DARLON I.; NOGUEIRA, CLAUDIO R.; MONTEIRO, AFIF F.; JULIANO, FERNANDA F.; DE ALENCAR, SEVERINO M.; PILLI, RONALDO A.; DE LIMA, CAROLINA A.; LONGATO, GIOVANNA B.; et al. Antiproliferative Flavanoid Dimers Isolated from Brazilian Red Propolis. Journal of Natural Products, v. 83, n. 6, p. 1784-1793, . (13/24416-1, 17/06014-4, 16/06137-6, 13/50228-8)
FREIRE, VITOR F.; GUBIANI, JULIANA R.; SPENCER, TARA M.; HAJDU, EDUARDO; FERREIRA, ANTONIO G.; FERREIRA, DAYANA A. S.; DE CASTRO LEVATTI, ERICA, V; BURDETTE, JOANNA E.; CAMARGO, CARLOS HENRIQUE; TEMPONE, ANDRE G.; et al. Feature-Based Molecular Networking Discovery of Bromopyrrole Alkaloids from the Marine Sponge Agelas dispar. Journal of Natural Products, v. 85, n. 5, p. 11-pg., . (19/17721-9, 17/06014-4, 20/03637-3, 13/50228-8, 21/04464-8)
BERLINCK, ROBERTO G. S.; MONTEIRO, AFIF F.; BERTONHA, ARIANE F.; BERNARDI, DARLON I.; GUBIANI, JULIANA R.; SLIVINSKI, JULIANO; MICHALISKI, LAMONIELLI F.; TONON, LUCIANE A. C.; VENANCIO, VICTOR A.; FREIRE, VITOR F.. Approaches for the isolation and identification of hydrophilic, light-sensitive, volatile and minor natural products. NATURAL PRODUCT REPORTS, v. 36, n. 7, p. 981-1004, . (16/21341-9, 17/06014-4, 16/14375-4, 16/11949-0, 13/50228-8, 17/25100-9)
GUBIANI, JULIANA R.; BERNARDI, DARLON I.; DE PAULA, CAIO C. P.; SELEGHIM, MIRNA H. R.; FERREIRA, ANTONIO G.; BATISTA, ANDREA N. L.; BATISTA, JOAO M.; OLIVEIRA, LUCIANNE F. P.; LIRA, SIMONE P.; BURDETTE, JOANNA E.; et al. Absolute configuration of cytotoxic anthraquinones from a Brazilian cave soil-derived fungus, Aspergillus sp. SDC28. ARCHIV DER PHARMAZIE, v. 355, n. 4, p. 8-pg., . (17/12436-9, 17/06014-4, 19/17721-9, 19/22319-5, 13/50228-8, 16/21341-9)
GUBIANI, J. R.; BANZATO, T. P.; NOGUEIRA, C. R.; MONTEIRO, A. F.; DE ALENCAR, S. M.; PILLI, R. A.; DE CARVALHO, J. E.; BERLINCKA, R. G. S.. Unprecedented isoflavanoid-neoflavonoid analogues isolated from Brazilian red propolis. Planta Medica, v. 85, n. 18, p. 1-pg., . (17/06014-4, 13/50228-8)

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