Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds

• Grant number: 15/17177-6
• Support type: BIOTA-FAPESP Program - Thematic Grants
• Duration: May 01, 2017 - April 30, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Leticia Veras Costa Lotufo
• Grantee: Leticia Veras Costa Lotufo
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Co-Principal Investigators: Glaucia Maria Machado Santelli
• Assoc. researchers: Gabriel Padilla ; Luiz Elidio Gregorio ; Marcelo José Pena Ferreira ; Marcio Adriano Andreo ; Norberto Peporine Lopes ; Paula Christine Jimenez ; Tito Monteiro da Cruz Lotufo ; Welington Luiz de Araújo
• Associated grant(s): 19/19506-8 - 7th International Conference on Food Factors (ICoFF2019) & the 12th International Conference and Exhibition on Nutraceuticals and Functional Foods (ISNFF2019), AR.EXT; 19/02008-5 - Marine compounds that induce DNA damage and inhibit TBX2 as a new strategy to treat breast cancer, AV.EXT; 18/08400-1 - Marine compounds that induce DNA damage and inhibit TBX2 as a new strategy to treat breast cancer, AP.R SPRINT; 17/19688-3 - Multi-user equipment approved in grant 2015/17177-6: lionheart fX automated live cell imager, AP.EMU
• Associated scholarship(s): 20/06613-8 - Characterization of seriniquinone mechanism of action in vemurafenibe resistant Melanoma cells, BP.DD; 20/09270-4 - Development of albumin nanoparticles as a vehicle of seriniquinone, BP.IC; 20/03795-8 - Participation in the maintenance of cell cultures in monolayer and 3D to assess the bioactivity of isolated substances in the development of Thematic Project 2015 / 17177-6, BP.TT; + associated scholarships 19/03008-9 - Chemical investigation on marine actinomycetes extracts with potential cytotoxic activity in tumoral lines and insecticide activity on Aedes aegypti species, BP.DR; 18/17595-0 - Study of pradimicina-IRD molecular interaction with DNA and its tumor cell mechanism of action, BP.DD; 18/25673-1 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds, BP.TT; 18/06522-2 - Use of bioaffinity chromatography in the prospecting of anticancer substances in marine actinomycetes: XIAP and STMN1 as pharmacological targets, BP.MS; 18/07661-6 - Seriniquinone and its derivative LT406 as antimelanoma agents in experimental models, BP.MS; 18/10071-6 - Influence of TBX2 expression on spheroid formation in human melanoma cell cultures, BP.IC; 17/18235-5 - Anticancer potential of isolated substances from Streptomyces SP. recovered from ascidian Euherdmania SP, BP.MS; 17/16606-6 - Actinomycetes from Brazilian islands: a metabolomic approach in bioprospecting natural products with antitumor potential, BP.PD; 17/09022-8 - Inhibitory Apoptosis Proteins (IAPs) as therapeutic targets in melanoma: studies with prodiginines in vemurafenibe-resistant cells, BP.PD; 17/17648-4 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds, BP.PD; 17/11285-7 - Study of the contribution of the inhibitory apoptosis protein survivin on effects of prodigiosin and derivatives in melanoma lineages, BP.IC - associated scholarships

Abstract

Brazilian marine ecosystems have great strategic importance for the country. Nonetheless, the sustainable use of marine natural resources is still a challenging endeavor. In fact, in many cases we even ignore what are the resources available, in view of the lack of information concerning biodiversity and ecosystems functioning. Thus, this project was conceived for the development of an integrative research strategy, in order to establish a new paradigm for bioprospection.I. Intellectual Merit: This proposal aims at providing an integrative approach to understand how diversity at different organization levels interact and may drive the production of secondary metabolites with interesting pharmacological properties, especially those related to cancer therapy. In particular, the leading premise is combining different approaches, including culture dependent (bioactivity and target-guided) and independent (metabolomics and metagenomics) studies, and also bring to context the underlying processes driving the biodiversity organization and functioning. The elected targets, the anti-senescence transcription factors Tbx2 and Tbx3, are involved in the tumorigenic process, but with no exogenous modulator described so far. The potential identification of new natural molecules from the Brazilian biodiversity targeting Tbx2 and Tbx3 bring to this project a strong innovative potential.II. Broader Impacts: Within the paradigm of sustainable use of natural resources, a core value in all diversity conservation programs, the integrative approach herein presented should be used for a comprehensive evaluation of emerging patterns driving diversity in different levels: from genes to secondary metabolites. III. Integration: The proposed integrative approach proposed brings together scientists from different research areas working under a common set of objectives, sharing data through electronic tools and brewing together ideas to promote knowledge on biodiversity conservation and sustainable use. It is worth mentioning, especially, that this project is essentially multidisciplinary and with great potential for innovation, as it is inserted in an extremely promising area, motivated by a sustainable exploration of marine resources in order to identify new biotechnological products, as well as to legitimize new anticancer molecular targets. (AU)

Scientific publications

(22)

(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)

TAVARES, MAURICIO TEMOTHEO; DE ALMEIDA, LARISSA COSTA; KRONENBERGER, THALES; FERREIRA, GLAUCIO MONTEIRO; DE DIVITIIS, THAINA FUJII; TOLEDO, MONICA FRANCO ZANNINI JUNQUEIRA; HASSIMOTTO, NEUZA MARIKO AYMOTO; MACHADO-NETO, JOAO AGOSTINHO; COSTA-LOTUFO, LETICIA VERAS; PARISE-FILHO, ROBERTO. Structure-activity relationship and mechanistic studies for a series of cinnamyl hydroxamate histone deacetylase inhibitors. Bioorganic & Medicinal Chemistry, v. 35, APR 1 2021. Web of Science Citations: 0.

PENA-HIDALGO, MIGUEL; FURTADO, LUCIANA COSTA; COSTA-LOTUFO, LETICIA V.; FERREIRA, MARCELO J. P.; SANTOS, DEBORAH Y. A. C. Alkaloids from the Leaves of Annona crassiflora and Their Cytotoxic Activity. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, APR 2021. Web of Science Citations: 0.

VICARI, HUGO PASSOS; LIMA, KELI; GOMES, RALPH DA COSTA; FERNANDES, DANIARA CRISTINA; LIPRERI DA SILVA, JEAN CARLOS; RODRIGUES JUNIOR, MANOEL TRINDADE; BARROSO DE OLIVEIRA, ALINE SILVA; DOS SANTOS, RICARDO NASCIMENTO; ANDRICOPULO, ADRIANO DEFINI; COELHO, FERNANDO; COSTA-LOTUFO, LETICIA VERAS; MACHADO-NETO, JOAO AGOSTINHO. Synthetic cyclopenta [b] indoles exhibit antineoplastic activity by targeting microtubule dynamics in acute myeloid leukemia cells. European Journal of Pharmacology, v. 894, MAR 5 2021. Web of Science Citations: 0.

AMBROSE, ANDREW J.; PHAM, NHAN T.; SIVINSKI, JARED; GUIMARAES, LARISSA; MOLLASALEHI, NILOUFAR; JIMENEZ, PAULA; ABAD, MARIA A.; JEYAPRAKASH, A. AROCKIA; SHAVE, STEVEN; COSTA-LOTUFO, LETICIA V.; LA CLAIR, JAMES J.; AUER, MANFRED; CHAPMAN, ELI. A two-step resin based approach to reveal survivin-selective fluorescent probes. RSC CHEMICAL BIOLOGY, v. 2, n. 1, p. 181-186, FEB 1 2021. Web of Science Citations: 0.

CARLOS, JORGE ANTONIO ELIAS GODOY; LIMA, KELI; COSTA-LOTUFO, LETICIA VERAS; LEITAO, ANDREI; MACHADO-NETO, JOAO AGOSTINHO. AD80, a multikinase inhibitor, exhibits antineoplastic effects in acute leukemia cellular models targeting the PI3K/STMN1 axis. INVESTIGATIONAL NEW DRUGS, JAN 2021. Web of Science Citations: 0.

TANGERINA, MARCELO M. P.; FURTADO, LUCIANA COSTA; LEITE, VIDA M. B.; BAUERMEISTER, ANELIZE; VELASCO-ALZATE, KAREN; JIMENEZ, PAULA C.; GARRIDO, LEANDRO M.; PADILLA, GABRIEL; LOPES, NORBERTO P.; COSTA-LOTUFO, LETICIA V.; PENA FERREIRA, MARCELO J. Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds. PLoS One, v. 15, n. 12 DEC 21 2020. Web of Science Citations: 0.

GIACONE, V, DANIELA; DARTORA, VANESSA F. M. C.; DE MATOS, JENYFFER K. R.; PASSOS, JULIA S.; MIRANDA, DANIEL A. G.; DE OLIVEIRA, ERICA A.; SILVEIRA, EDILBERTO R.; COSTA-LOTUFO, V, LETICIA; MARIA-ENGLER, SILVYA S.; LOPES, LUCIANA B. Effect of nanoemulsion modification with chitosan and sodium alginate on the topical delivery and efficacy of the cytotoxic agent piplartine in 2D and 3D skin cancer models. International Journal of Biological Macromolecules, v. 165, n. A, p. 1055-1065, DEC 15 2020. Web of Science Citations: 2.

TAKAYASU, BIANCA S.; MARTINS, IGOR R.; GARNIQUE, ANALI M. B.; MIYAMOTO, SAYURI; MACHADO-SANTELLI, GLAUCIA M.; UEMI, MIRIAM; ONUKI, JANICE. Biological effects of an oxyphytosterol generated by beta-Sitosterol ozonization. Archives of Biochemistry and Biophysics, v. 696, DEC 15 2020. Web of Science Citations: 0.

BRANCO, PAOLA C.; PONTES, CRISTINE A.; REZENDE-TEIXEIRA, PAULA; AMENGUAL-RIGO, PEP; ALVES-FERNANDES, DEBORA K.; MARIA-ENGLER, SILVYA STUCHI; DA SILVA, ALISON B.; PESSOA, OTILIA DEUSDENIA L.; JIMENEZ, PAULA C.; MOLLASALEHI, NILOUFAR; CHAPMAN, ELI; GUALLAR, VICTOR; MACHADO-NETO, JOAO.; COSTA-LOTUFO, LETICIA V. Survivin modulation in the antimelanoma activity of prodiginines. European Journal of Pharmacology, v. 888, DEC 5 2020. Web of Science Citations: 0.

WILKE, V, DIEGO; JIMENEZ, PAULA C.; BRANCO, PAOLA C.; REZENDE-TEIXEIRA, PAULA; TRINDADE-SILVA, AMARO E.; BAUERMEISTER, ANELIZE; LOPES, NORBERTO PEPORINE; COSTA-LOTUFO, V, LETICIA. Anticancer Potential of Compounds from the Brazilian Blue Amazon. Planta Medica, v. 87, n. 01/02 NOV 2020. Web of Science Citations: 0.

ELIAS GODOY CARLOS, JORGE ANTONIO; LIMA, KELI; COELHO-SILVA, JUAN LUIZ; ALVES-PAIVA, RAQUEL DE MELO; MORENO, NATALIA CESTARI; VICARI, HUGO PASSOS; DE SOUZA SANTOS, FABIO PIRES; HAMERSCHLAK, NELSON; COSTA-LOTUFO, LETICIA VERAS; TRAINA, FABIOLA; MACHADO-NETO, JOAO AGOSTINHO. Reversine exerts cytotoxic effects through multiple cell death mechanisms in acute lymphoblastic leukemia. CELLULAR ONCOLOGY, v. 43, n. 6 AUG 2020. Web of Science Citations: 0.

SAHM, BIANCA DEL B.; PERES, JADE; REZENDE-TEIXEIRA, PAULA; SANTOS, EVELYNE A.; BRANCO, PAOLA C.; BAUERMEISTER, ANELIZE; KIMANI, SERAH; MOREIRA, EDUARDA A.; BISI-ALVES, RENATA; BELLIS, CLAIRE; MLAZA, MIHLALI; JIMENEZ, PAULA C.; LOPES, NORBERTO P.; MACHADO-SANTELLI, GLAUCIA M.; PRINCE, SHARON; COSTA-LOTUFO, V, LETICIA. Targeting the Oncogenic TBX2 Transcription Factor With Chromomycins. FRONTIERS IN CHEMISTRY, v. 8, MAR 3 2020. Web of Science Citations: 0.

BARROSO, CRISTIANE XEREZ; PEREIRA DE FREITAS, JOAO EDUARDO; MATTHEWS-CASCON, HELENA; ARRUDA BEZERRA, LUIS ERNESTO; DA CRUZ LOTUFO, TITO MONTEIRO. Molecular evidences confirm the taxonomic separation of two sympatric congeneric species (Mollusca, Gastropoda, Neritidae, Neritina). ZOOKEYS, n. 904, p. 117-130, JAN 16 2020. Web of Science Citations: 0.

JIMENEZ, PAULA C.; WILKE, DIEGO V.; BRANCO, PAOLA C.; BAUERMEISTER, ANELIZE; REZENDE-TEIXEIRA, PAULA; GAUDENCIO, SUSANA P.; COSTA-LOTUFO, LETICIA V. Enriching cancer pharmacology with drugs of marine origin. British Journal of Pharmacology, v. 177, n. 1, p. 3-27, JAN 2020. Web of Science Citations: 1.

PINTO, FRANCISCO C. L.; SILVEIRA, EDILBERTO R.; VASCONCELOS, ANA CAROLINE L.; FLORENCIO, KATHARINE G. D.; OLIVEIRA, FRANCISCA A. S.; SAHM, BIANCA B.; COSTA-LOTUFO, V, LETICIA; BAUERMEISTER, ANELIZE; LOPES, NORBERTO P.; WILKE, V, DIEGO; PESSOA, OTILIA D. L. Dextrorotatory Chromomycins from the Marine Streptomyces sp. Associated to Palythoa caribaeorum. Journal of the Brazilian Chemical Society, v. 31, n. 1, p. 143-152, JAN 2020. Web of Science Citations: 0.

MARIACATERINA LIANZA; MARIA HELENA VERDAN; JEAN PAULO DE ANDRADE; FERRUCCIO POLI; LARISSA C. DE ALMEIDA; LETICIA V. COSTA-LOTUFO; ÁLVARO CUNHA NETO; SARAH C. C. OLIVEIRA; JAUME BASTIDA; ANDREA N. L. BATISTA; JOÃO M. BATISTA JR.; WARLEY S. BORGES. Isolation, Absolute Configuration and Cytotoxic Activities of Alkaloids from Hippeastrum goianum (Ravenna) Meerow (Amaryllidaceae). Journal of the Brazilian Chemical Society, v. 31, n. 10, p. 2135-2145, Out. 2020. Web of Science Citations: 0.

VELASCO-ALZATE, KAREN Y.; BAUERMEISTER, ANELIZE; TANGERINA, MARCELO M. P.; LOTUFO, TITO M. C.; FERREIRA, MARCELO J. P.; JIMENEZ, PAULA C.; PADILLA, GABRIEL; LOPES, NORBERTO P.; COSTA-LOTUFO, LETICIA V. Marine Bacteria from Rocas Atoll as a Rich Source of Pharmacologically Active Compounds. MARINE DRUGS, v. 17, n. 12 DEC 2019. Web of Science Citations: 0.

DE ALMEIDA, LARISSA COSTA; BAUERMEISTER, ANELIZE; REZENDE-TEIXEIRA, PAULA; DOS SANTOS, EVELYNE ALVES; BERALDO DE MORAES, LUIZ ALBERTO; MACHADO-NETO, JOAO AGOSTINHO; COSTA-LOTUFO, LETICIA VERAS. Pradimicin-IRD exhibits antineoplastic effects by inducing DNA damage in colon cancer cells. Biochemical Pharmacology, v. 168, p. 38-47, OCT 2019. Web of Science Citations: 1.

MEDINA, REBECA P.; ARAUJO, ANGELA R.; BATISTA JR, JOAO M.; CARDOSO, CARMEN L.; SEIDL, CLAUDIA; VILELA, ADRIANA F. L.; DOMINGOS, V, HELORI; COSTA-LOTUFO, V, LETICIA; ANDERSEN, RAYMOND J.; SILVA, DULCE H. S. Botryane terpenoids produced by Nemania bipapillata, an endophytic fungus isolated from red alga Asparagopsis taxiformis - Falkenbergia stage. SCIENTIFIC REPORTS, v. 9, AUG 23 2019. Web of Science Citations: 1.

DA SILVA, ALISON B.; SILVEIRA, EDILBERTO R.; WILKE, DIEGO V.; FERREIRA, ELHTON G.; COSTA-LOTUFO, LETICIA V.; TORRES, MARIA CONCEICAO M.; AYALA, ALEJANDRO PEDRO; COSTA, WENDELL S.; CANUTO, KIRLEY M.; DE ARAUJO-NOBRE, ALYNE R.; ARAUJO, ANA JERSIA; MARINHO FILHO, JOSE DELANO B.; PESSOA, OTILIA DEUSDENIA L. Antibacterial Salinaphthoquinones from a Strain of the Bacterium Salinispora arenicola Recovered from the Marine Sediments of St. Peter and St. Paul Archipelago, Brazil. Journal of Natural Products, v. 82, n. 7, p. 1831-1838, JUL 2019. Web of Science Citations: 4.

INDY TAMAYOSE, CINTHIA; DOS SANTOS, EVELYNE A.; ROQUE, NADIA; COSTA-LOTUFO, LETICIA V.; PENA FERREIRA, MARCELO J. Caffeoylquinic Acids: Separation Method, Antiradical Properties and Cytotoxicity. CHEMISTRY & BIODIVERSITY, v. 16, n. 7 JUL 2019. Web of Science Citations: 1.

BAUERMEISTER, ANELIZE; VELASCO-ALZATE, KAREN; DIAS, TIAGO; MACEDO, HELENA; FERREIRA, ELTHON G.; JIMENEZ, PAULA C.; LOTUFO, TITO M. C.; LOPES, NORBERTO P.; GAUDENCIO, SUSANA P.; COSTA-LOTUFO, V, LETICIA. Metabolomic Fingerprinting of Salinispora From Atlantic Oceanic Islands. FRONTIERS IN MICROBIOLOGY, v. 9, DEC 11 2018. Web of Science Citations: 3.