Development of inhibitors and fluorescent probes for the enzyme Lysine specific demethylase (LSD1)

• Grant number: 14/03812-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2014
• End date: February 29, 2016
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Flavio da Silva Emery
• Grantee: Miguel de Menezes Vaidergorn
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The pathogenesis of several diseases may be involved in changes in the structural and functional state of chromatin due to epigenetic changes . The histone lysine - specific demethylase (LSD1) is closely related to several both physiological and pathological processes such as tumorigenesis and viral infections , which leads to a target of interest for the discovery of bioactive compounds that act on epigenetic processes . Tranylcypromine is known since the late 1940s and was used as an inhibitor of MAO up to discover that this compound and its derivatives are associated with the prevention and treatment of diseases and conditions associated with LSD histone activities , as well as diseases characterized by deregulation in gene transcription , cell differentiation and proliferation. However, due to its structure, this molecule shows moderate activity and low selectivity regarding LSD enzyme in study. In this context , the theme of this work is the preparation of a library of compounds based on spatial configuration of tranylcypromine , thus seeking potential molecules with greater selectivity and biological activity , and also the preparation of fluorescent probes in order to better understand the active site of LSD.

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)

VAIDERGORN, MIGUEL M.; CARNEIRO, ZUMIRA A.; LOPES, CARLA D.; DE ALBUQUERQUE, SERGIO; REIS, FELIPE C. C.; NIKOLAOU, SOFIA; E MELLO, JULIANA F. R.; GENESI, GIOVANI L.; TROSSINI, GUSTAVO H. G.; GANESAN, A.; et al. beta-amino alcohols and their respective 2-phenyl-N-alkyl aziridines as potential DNA minor groove binders. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 157, p. 657-664, SEP 5 2018. (15/20302-7, 14/03812-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

VAIDERGORN, Miguel de Menezes. Developtment of a library of ?-amino alcohols and aziridines with potential antitumoral activity. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.