title: Caco-2 cells permeability evaluation of nifuroxazide derivatives with potential activity against methicillin-resistant Staphylococcus aureus (MRSA).
abstract: Throughout the period of evaluation and selection in drug development, the assessment of the permeability potential of a compound to achieve an efficient refinement of the molecular structure has been widely appraised by the transport of substances across cell monolayers. This study aims to develop in vitro assays through Caco-2 cells in order to analyze the permeability of 5-nitro-heterocyclic compounds analogues to nifuroxazide with antimicrobial activity, especially showing promising activity against multidrug-resistant Staphylococcus aureus (MRSA). Caco-2 cell monolayers cultivated for 21 days in Transwell® plates were used for the in vitro permeability assays. The quantification of the nifuroxazide derivatives in the basolateral chambers was performed by a validated high performance liquid chromatography with UV (HPLC-UV) method. Apparent permeability values (Papp) show that these compounds can be considered as new drug candidates with the potential to present high absorption in vivo, according to the classifications of Yee and Biganzoli. The thiophenic derivatives showed permeability values higher than the furanic ones, being AminoTIO the compound with the greatest potential for the development of a new drug against MRSA, since it showed the best cytotoxicity, permeability and solubility ratio among all the derivatives.
authors.affiliation: Pharmacy Department, Pharmaceutical Sciences Faculty, University of São Paulo , São Paulo - SP , Brazil and.
authors.forename: Mariane
authors.initials: M
authors.lastname: B Fernandes
authors.forename: José E
authors.initials: JE
authors.lastname: Gonçalves
authors.forename: Leoberto
authors.initials: L
authors.lastname: C Tavares
authors.forename: Sílvia
authors.initials: S
authors.lastname: Storpirtis
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D062385:Hydroxybenzoates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D009581:Nitrofurans / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010539:Permeability; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000890:Anti-Infective Agents; D062385:Hydroxybenzoates; D009581:Nitrofurans; C013150:nifuroxazide
keywords: 5-Nitro-heterocyclic; anti-infectives; biopharmacy; drug development; intestinal absorption