Synthesis and study of the hemolytic activity of alkyl benzyl ether analogs of erufosine

• Grant number: 14/07811-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2014
• End date: March 31, 2016
• Field of knowledge: Health Sciences - Pharmacy
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Carlota de Oliveira Rangel Yagui
• Grantee: Luciana de Moura Bueno
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer is a group of diseases characterized by genetic alterations that cause to excessive and uncontrolled cellular growth, resulting in a tumor mass. The current chemotherapeutic options are usually associated to cytotoxicity and damage to healthy cells, compromising organs not affected by the disease. Alkylphospholipids, on the other hand, can be considered a promising class of antitumor agents, with the mechanism of action proposed related to cell membrane interaction and protein kinases inhibition. The prototype of Alkylphophocholines (APC), a subclass of APL, is miltefosine, drug already approved for cutaneous metastasis of breast cancer. However, miltefosine presents gastrointestinal toxicity and hemolytic activity. More recently, a miltefosine analog, erucylphosphocholine, was synthesized and represented an important progress since this drug can be employed intravenously. Its homocholinic analog, erufosine, presents even lower hemolytic activity and can be considered as a promising chemical structure. In this project, we will synthesize benzyl alkyl ether analogs of erufosine, as well as investigate it hemolytic activity. The compounds planned will be obtained based on the synthesis of w-hydroxybenzylalkyl ethers as intermediates, which will be employed in a new synthetic route comprising four steps. The w-hydroxybenzylalkyl ethers will react with phosphorous oxychloride and, subsequently, with N-methylpropanolamine. Finally, an N-methylation step will be carries out employing methyl iodide, to obtain the analogs planned. The hemolytic activity of the compounds obtained will be investigated. Based on the results of this project, the antiproliferative activity of the compounds may be carried out in the future. (AU)

Academic Publications

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

BUENO, Luciana de Moura. Study of the synthesis of benzyl alkyl ether analogs of miltefosine and erufosine.. 2016. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.