St George's University of London, UK.
Tuberculosis (Edinb). 2010 Sep;90(5):301-5. doi: 10.1016/j.tube.2010.07.004. Epub 2010 Aug 21.
The bactericidal activities of the diarylquinoline TMC207 in a liquid culture medium started with a bacteriostatic phase lasting about 7 days and then continued with a dose-related bactericidal phase. In comparison, its intra-cellular activity in primary mouse peritoneal macrophages (PM) and in the J774 macrophage-like cell line had little or no static phase so that the bactericidal kill was evident by 5-7 days presumably due to low bacterial ATP levels. Bactericidal activities in the three systems were compared by estimating the rate of bacterial killing (K) during exposure to 0.12-1.0 μg/ml TMC207 which were similar at, -0.35 in the J774 cells and -0.27 in mouse PM (p = 0.6) with each lower than -0.11 in extra-cellular cultures (p < 0.001) and [2] the TMC207 concentration at the intersection between the curve relating cfu count to TMC207 concentration and the cfu count at day-0, defined as the static concentration. Static concentrations were 0.22 μg/ml for extra-cellular cultures, 0.17 μg/ml for mouse PM and 0.06 μg/ml for J774 cells, significantly lower than the extra-cellular value (p < 0.001). Thus, the intra-cellular activity of TMC207 is clearly greater than its extra-cellular activity mainly because the preliminary static phase was a shorter or absent.
二芳基喹啉 TMC207 在液体培养基中的杀菌活性首先经历一个持续约 7 天的抑菌阶段，然后继续进行剂量相关的杀菌阶段。相比之下，TMC207 在原代小鼠腹腔巨噬细胞 (PM) 和 J774 巨噬样细胞系中的细胞内活性几乎没有或没有静止期，因此在 5-7 天内就表现出杀菌作用，这可能是由于细菌的 ATP 水平较低。通过估计在 0.12-1.0 μg/ml TMC207 暴露下细菌的杀菌速度 (K) 来比较三种系统中的杀菌活性，在 J774 细胞和小鼠 PM 中分别为 -0.35 和 -0.27，均低于细胞外培养物中的 -0.11 (p < 0.001)，并且 [2] TMC207 浓度在与 TMC207 浓度相关的细菌计数曲线和第 0 天细菌计数的交点处，定义为静止浓度。细胞外培养物的静止浓度为 0.22 μg/ml，小鼠 PM 为 0.17 μg/ml，J774 细胞为 0.06 μg/ml，明显低于细胞外值 (p < 0.001)。因此，TMC207 的细胞内活性明显大于其细胞外活性，主要是因为初步的静止期较短或不存在。
