Investigation of cytotoxic mechanisms of synthetic derivatives of seriniquinone in melanoma cell lines

• Grant number: 16/10854-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2016
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• 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

Abstract

Cancer is the leading cause of death in the world nowadays, making it essential to develop new treatments. Several therapeutic targets have been exploited from the knowledge of the molecular basis of tumorigenesis and the DCD gene, which produces the protein dermcidin, is an example that has been studied more recently. Therefore, its role in cancer is poorly understood with only some evidences related to proliferation, migration, invasion, cell survival and resistance. By the screening of secondary metabolites from marine bacteria, it was isolated seriniquinone compound from Serinicoccus genus, which targets the protein dermcidin, regulating its expression and inducing cell death by autophagy selectively in melanoma cell lines. Given these promising results, 4 structural analogues of seriniquinone were synthesized in order to increase their cytotoxicity and selectivity for melanoma cells and to improve pharmacokinetic factors. In view of this, this project aims to evaluate the mechanisme underlying the cytotoxicity of these molecules in melanoma cell lines and the relationship of the cytotoxic properties with dermcidin regulation.

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)