Synthesis and biological evaluation of lysine specific demethylase 1 (LSD-1)

• Grant number: 16/13154-4
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2016
• Effective date (End): August 31, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Flavio da Silva Emery
• Grantee: Fernanda Mika Nomizo
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Cancer is a disease that has affected thousands of people over the years. Epigenetics studies have shown that the superexpression of the enzyme lysine-specific demethylase 1 (LSD-1) is involved with the development of some types of cancer, as prostate, and bladder cancer. This correlation between LSD-1 and cancer growth and progression made LSD-1 become a potential target to find new therapeutics for this disease. The first described LSD-1 inhibitor was tranylcypromine, which was originally used as an inhibitor of the enzyme monoamine oxidase (MAO). Analogs of tranylcypromine, peptides based inhibitors and polyamines were also described as LSD-1 inhibitors. In order to develop a selective and potent inhibitor of this enzyme, our research group used virtual screening techniques based on the LSD-1 structure to obtain compounds with possible inhibitory action. One of the obtained compounds was chosen as a hit to be used for the development of this proposal. In this context, this proposal targets the synthesis of the hit compound and a library of analogues, studying the best synthetic approach, and the biologic evaluation of the inhibitory action of the library of compounds.