Design and synthesis of hybrids of belinostat and sorafenib

• Grant number: 19/14242-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2020
• End date: December 31, 2020
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Roberto Parise Filho
• Grantee: Thainá Fujii de Divitiis
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer is a group of diseases that involves abnormal cell growth, with the potential to invade or spread to other parts of the body. Studies show that the overexpression of tyrosine kinases (TK) and epigenetic factors are characteristic of cancer, being the deacetylation of histones one of the main mechanisms. Therefore, TK and enzyme deacetylase (HDAC) inhibitors, which reestablish intracellular homeostasis, are of great interest in therapeutics. In this context, target-specific therapy, which refers to the use of drugs that are designed to interact with a specific molecular target, is framed, which tends to decrease the cytotoxicity of the treatment as compared to the current treatments. This project, through molecular hybridization, proposes the design and synthesis of new molecules, based on the structural framework of the drugs sorafenib (TKi) and belinostat (HDACi), which will be submitted to a cytotoxicity test in order to obtain chemical entities with potential dual action for the treatment of cancer.