title: Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA).
abstract: It is important to determine the toxicity of compounds and co-solvents that are used in cell monolayer permeability studies to increase confidence in the results obtained from these in vitro experiments. This study was designed to evaluate the cytotoxicity of new nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA) in Caco-2 cells to select analogues for further in vitro permeability analyses. In this study, nitrofurantoin and nifuroxazide, in addition to 6 furanic and 6 thiophenic nifuroxazide derivatives were tested at 2, 4, 6, 8 and 10 μg/mL. In vitro cytotoxicity assays were performed according to the MTT (methyl tetrazolium) assay protocol described in ISO 10993-5. The viability of treated Caco-2 cells was greater than 83% for all tested nitrofurantoin concentrations, while those treated with nifuroxazide at 2, 4 and 6 μg/mL had viabilities greater than 70%. Treatment with the nifuroxazide analogues resulted in viability values greater than 70% at 2 and 4 μg/mL with the exception of the thiophenic methyl-substituted derivative, which resulted in cell viabilities below 70% at all tested concentrations. Caco-2 cells demonstrated reasonable viability for all nifuroxazide derivatives, except the thiophenic methyl-substituted compound. The former were selected for further permeability studies using Caco-2 cells.
authors.affiliation: Pharmaceutical Sciences Faculty, Pharmacy Department, University of São Paulo, Av. Prof. Lineu Prestes, 580, bl. 13, Cidade Universitária, 05508-900 São Paulo, SP, Brazil. M.FERNANDES@USP.BR
authors.forename: Mariane B
authors.initials: MB
authors.lastname: Fernandes
authors.forename: José E
authors.initials: JE
authors.lastname: Gonçalves
authors.forename: Marcus T
authors.initials: MT
authors.lastname: Scotti
authors.forename: Alex A
authors.initials: AA
authors.lastname: de Oliveira
authors.forename: Leoberto C
authors.initials: LC
authors.lastname: Tavares
authors.forename: Sílvia
authors.initials: S
authors.lastname: Storpirtis
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D062385:Hydroxybenzoates / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D009581:Nitrofurans / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D009582:Nitrofurantoin / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000890:Anti-Infective Agents; D062385:Hydroxybenzoates; D009581:Nitrofurans; D009582:Nitrofurantoin; C013150:nifuroxazide