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
• Start date: June 01, 2017
• End date: July 31, 2020
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Agreement: 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

Abstract

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)

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)

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., 2022-05-27. (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, JUL 1 2019. (16/21341-9, 17/06014-4, 16/14375-4, 16/11949-0, 13/50228-8, 17/25100-9)

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, JUN 26 2020. (13/24416-1, 17/06014-4, 16/06137-6, 13/50228-8)

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., 2019-12-01. (17/06014-4, 13/50228-8)

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., 2022-04-01. (20/15230-5, 17/06014-4, 19/26210-8)

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., 2022-01-31. (17/12436-9, 17/06014-4, 19/17721-9, 19/22319-5, 13/50228-8, 16/21341-9)

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, OCT 2021. (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, NOV 2021. (13/50741-7, 16/14375-4, 16/05133-7, 17/06014-4, 13/50228-8, 16/21341-9, 19/00447-1)

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, SEP 2018. (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, JAN 2020. (13/23153-7, 16/21341-9, 17/06014-4, 13/50228-8, 16/16033-3)

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, OCT 2020. (13/07600-3, 17/06014-4)

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., 2023-04-29. (17/06014-4, 14/50926-0)