Pharmaceutical Sciences Faculty, Pharmacy Department, University of São Paulo, Av. Prof. Lineu Prestes, 580, bl. 13, Cidade Universitária, 05508-900 São Paulo, SP, Brazil.
Toxicol In Vitro. 2012 Apr;26(3):535-40. doi: 10.1016/j.tiv.2012.01.018. Epub 2012 Jan 21.
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.
确定用于细胞单层渗透性研究的化合物和共溶剂的毒性对于增加对这些体外实验结果的信心非常重要。本研究旨在评估具有抗耐甲氧西林金黄色葡萄球菌（MRSA）活性的新型硝呋太尔衍生物在 Caco-2 细胞中的细胞毒性，以选择用于进一步体外渗透性分析的类似物。在这项研究中，除了 6 个呋喃和 6 个噻吩硝呋太尔衍生物外，还在 2、4、6、8 和 10μg/mL 下测试了硝呋太因和硝呋太尔。根据 ISO 10993-5 中描述的 MTT（甲基噻唑基四唑）测定方案进行体外细胞毒性测定。用所有测试的硝呋太因浓度处理的 Caco-2 细胞的存活率均大于 83%，而用 2、4 和 6μg/mL 的硝呋太尔处理的细胞的存活率大于 70%。除噻吩甲基取代衍生物外，用硝呋太尔类似物处理时，在 2 和 4μg/mL 时的存活率大于 70%，而噻吩甲基取代衍生物在所有测试浓度下的细胞存活率均低于 70%。除噻吩甲基取代化合物外，Caco-2 细胞对所有硝呋太尔衍生物均表现出合理的活力。选择这些化合物进行进一步的 Caco-2 细胞渗透性研究。
