IN VITRO PERMEABILITY OF A NEW NIFUROXAZIDE DERIVATIVE WITH ACTIVITY AGAINST MULTIDRUG-RESISTANT STRAINS OF STAPHYLOCOCCUS AUREUS USING CACO-2 CELLS

• Grant number: 11/14624-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2011
• End date: September 30, 2012
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Silvia Storpirtis
• Grantee: Adriana Cogo Malgueiro
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

During the search for new drugs with potential antimicrobial activity, the 5-nitro-heterocyclic nifuroxazide derivatives have shown activity against multidrug-resistant strains of Staphylococcus aureus. Since the oral route is the preferred one for the administration of drugs, estimating the human bioavailability of oral drug candidates in the early stages of the development process is important and necessary for efficient selection and optimization. Among the many absorption models in cell culture in vitro, the most used are the Caco-2 cells. These are cancer cells derived from human colorectal cancer, which present the majority of morphological and functional properties of cells in the human intestinal epithelium. Many studies have shown that human oral absorption is related to the permeability through Caco-2 cells. Many studies have shown that the human oral absorption of compounds is related to their apparent permeability (Papp) calculated by quantifying the permeated fraction through the monolayer of Caco-2 cells as a function of time. Therefore, the permeability through these cells is a valuable index to estimate the uptake of compounds by oral administration. In this context, this project aims to develop in vitro assays using Caco-2 cells to examine the permeability of a new 5-nitro-heterocyclic compound with antimicrobial activity, mainly showing promising activity against multidrug-resistant strains of Staphylococcus aureus.