Seriniquinone and its derivative LT406 as antimelanoma agents in experimental models

• Grant number: 18/07661-6
• Support type: 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
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal researcher: Leticia Veras Costa Lotufo
• Grantee: Amanda Soares Hirata
• Home 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)

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, FEB 2019. (16/10854-5, 18/07661-6)