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Seriniquinone and its derivative LT406 as antimelanoma agents in experimental models

Grant number: 18/07661-6
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2018
Effective date (End): September 30, 2020
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Leticia Veras Costa Lotufo
Grantee:Amanda Soares Hirata
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds, AP.BTA.TEM

Abstract

Cancer is the second leading cause of death in the world today, making important the development of new drugs and the study of the molecular bases of tumorigenesis. Through bioprospection of secondary metabolites of microorganisms, seriniquinone (SQ) was isolated from a marine bacterium of the genus Serinicoccus. Further studies have shown that SQ regulates the expression of the dermicidin gene (DCD), a protein which function is not understood yet in neoplasia, and induces cell death by autophagy with selectivity for melanoma cells, the most aggressive skin cancer. More recent studies with the synthetic derivative of SQ named LT406, it has been evaluated cytotoxicity, colony formation and cell cycle in melanoma lines with the most recurrent mutations: BRAFV600E and NRAS. With promising results, both substances showed antitumor potential and more studies of the mechanism of action are required. In addition, the present project will also address the treatment of melanoma cells that are resistant to vemurafenib (PLX4032), a drug used today in the clinic where chemoresistance is highly reported. In vitro assays will be performed to evaluate the toxicity and mechanism of action with special emphasis on the participation of the dermicidin protein in the mechanisms of chemoresistance and SQ action. In vivo studies will also be performed through xenographic model. (AU)

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Scientific publications
(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)
HAMMONS, JUSTIN C.; TRZOSS, LYNNIE; JIMENEZ, PAULA C.; HIRATA, AMANDA S.; COSTA-LOTUFO, LETICIA V.; LA CLAIR, JAMES J.; FENICAL, WILLIAM. Advance of Seriniquinone Analogues as Melanoma Agents. ACS Medicinal Chemistry Letters, v. 10, n. 2, p. 186-190, . (16/10854-5, 18/07661-6)
APOLINARIO, ALEXSANDRA CONCEICAO; HIRATA, AMANDA SOARES; ANJOS MIGUEL, RODRIGO DOS; COSTA-LOTUFO, LETICIA VERAS; PESSOA, ADALBERTO; LA CLAIR, JAMES J.; FENICAL, WILLIAM; LOPES, LUCIANA BIAGINI. Exploring the benefits of nanotechnology for cancer drugs in different stages of the drug development pipeline. Nanomedicine, v. 15, n. 26, p. 4-pg., . (18/13877-1, 15/17177-6, 18/07661-6, 18/14375-0)

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Filed patent(s) as a result of this research project

PROCESSO DE OBTENÇÃO DE SISTEMAS NANOESTRUTURADOS, CRISTAIS LÍQUIDOS DO TIPO LAMELAR DE FORMA ESTÁVEL, USO DOS REFERIDOS CRISTAIS LÍQUIDOS, PROCESSO DE OBTENÇÃO DE NANOPARTÍCULAS DE ALBUMINA, AS REFERIDAS NANOPARTÍCULAS DE ALBUMINA E USOS DAS NANOPARTÍCULAS DE ALBUMINA BR1020210222808 - Universidade de São Paulo (USP) . LUCIANA BIAGINI LOPES, ALEXSANDRA CONCEIÇÃO APOLINÁRIO, RODRIGO DOS ANJOS MIGUEL, KELLY ISHIDA, VINÍCIUS MORAIS BARROSO, AMANDA SOARES HIRATA, LETICIA VERAS COSTA LOTUFO - November 2021, 05