In vitro evaluation of anti-tumor effects of benzofuroxan derivatives in cell lines of malignant melanoma

• Grant number: 16/09706-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2016
• End date: July 31, 2017
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Salomão Dória Jorge
• Grantee: Caroline dos Santos Moraes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Melanoma is a malignant tumor that develops from abnormal and uncontrolled proliferation of melanocytes. The incidence of this cancer has been growing constantly, representing a serious public health problem due to its aggressiveness due to the high capacity of spread and resistance to chemotherapy. Due to the relative failure of the existing current treatments for metastatic melanoma, there is an urgent need for development of new drugs that may be useful in the treatment of this cancer. In this context, it cites candidates for antitumor drugs based on benzofuroxanos binders, able to inhibit the BRAF protein. The BRAF protein is a serine / threonine kinase that participates in a signaling cascade of MAPK (Mitogen-Activated Protein Kinase), considered the main signaling cascade involved in the proliferation, migration and control the growth of the cell population. This pathway is related to the development and maintenance of cutaneous melanoma due to deregulation of the signaling cascade and mutations that lead to hyperactivation of the pathway, generating an uncontrolled cell proliferation process. Point mutations, found in over 70% of melanoma cases, may transform a BRAF oncogene. Thus, the mutated BRAF protein is a promising therapeutic target, reinforcing the importance of developing a new class of drugs with potential anti-tumor effect that act selectively on this protein. The proposal of this project is to evaluate the in vitro anti-tumor effects of new derivatives benzofuroxanos in cell lines of melanoma.