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In vitro metabolism study of salt of the acid lasalocid using hepatic microsomes

Grant number: 13/15205-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2013
Effective date (End): November 30, 2015
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal researcher:Norberto Peporine Lopes
Grantee:Fernando Armani Aguiar
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The discovery of new drugs is deeply connected to innovations in the chemistry, pharmacology, molecular and cell biology, which improve the understanding of biochemical and physiological pathways, and molecular targets, making possible the discovery of new assets. Amid the technology advances in combinatorial synthesis and the use of high-throughput screening, a decrease by the pharmaceutical industry to develop drugs of natural origin was observed. However, with the decrease in the number of new drugs launched in the market in the past two decades, the pharmaceutical industry has been interested to reconsider natural products with proven biological activity in new targets. The lasalocid (commercial salt of lasalocid acid) is a carboxylic ionophore produced by Streptomyces lasaliensis. Ionophores are also classified as polyether antibiotics and exhibit a broad spectrum of bioactivity, varying from antibacterial to antiviral and, more recently, its cytotoxicity in tumor cells was discovered. Although widely used in veterinary products little is known of the phase 1 metabolism of this substance. The vast majority of research aimed at developing analytical methods for quality control of products of animal origin in order to meet the demands of regulatory processes. As mentioned above, the ionophore of this project showed a promising antitumor activity, which, along with the lack of data on its metabolism in the face of cytochrome P450 enzymes in rats and humans, stimulates further investigation. In this context, this project aims to determine the enzimatic kinetic parameters of the lasalocid in vitro and its possible metabolites formed using hepatic microsomes for both humans and rats.