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HY152-J(1)是一个体外具有抗耐药结核活性的候选化合物。本试验建立了Caco-2细胞单层模型,采用LCMS/MS法考察了1与转运蛋白P-gp的相互作用。结果表明,用于转运试验的Caco-2细胞能够形成致密、完整以及功能良好的均匀单层细胞;不同浓度1从基底侧(BL)到肠腔侧(AP)的表观渗透系数与AP到BL的表观渗透系数的比值(P_(app,BL-AP)/P_(app,AP-BL))为0.99~1.27,提示1很可能不是P-gp的底物;与阴性对照组相比,1在0.625~10mmol/L范围内并没有显著降低Caco-2细胞单层模型中地高辛的外排比(ER值),据此初步推断1并非P-gp的抑制剂。
HY152-J (1) is a candidate compound with anti-TB activity in vitro. In this study, a Caco-2 cell monolayer model was established and the interaction between 1 and P-gp transporter was investigated by LCMS / MS. The results showed that Caco-2 cells used for transport assay could form uniform, monolayer cells with dense, intact and well-functioned cells. The apparent permeability coefficients of basal side (BL) to the luminal side (AP) The ratio of apparent permeability coefficient of BL (P_ (app, BL-AP) / P_ (app, AP-BL)) was 0.99-1.27, suggesting that 1 is probably not the substrate of P-gp. Compared with the negative control group , 1 in 0.625 ~ 10mmol / L did not significantly reduce the Caco-2 cell monolayer model of digoxin excretion ratio (ER), suggesting that 1 is not P-gp inhibitor.