University of Rome Tor Vergata, Rome, Italy.
Antiviral Res. 2011 Nov;92(2):255-61. doi: 10.1016/j.antiviral.2011.08.008. Epub 2011 Aug 16.
The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, in order to determine their relative potency and efficacy in different cellular systems of HIV infection. Raltegravir showed better protective efficacy in all cell types; MK-2048, L870,810 and IN5 showed a potent anti-HIV-1 activity in macrophages, while in lymphocytes only MK-2048 and L870,810 showed an inhibitory effect comparable to raltegravir. IN2 was a poorly effective anti-HIV-1 compound in all cellular systems. All effective integrase inhibitors exhibited a potent antiviral activity against both X4 and R5 HIV-1 strains. In general, raltegravir, MK-2048, L870,810 and IN5 showed anti HIV activity similar or slightly higher in macrophages compared to PBMC and C8166 T cells: for MK-2048, the EC(50) was 0.4, 0.9, 11.5 nM in macrophages, in PBMCs and T cells, respectively; for L870,810, the EC(50) was 1.5, 14.3, and 10.6 nM, respectively; for IN5 the EC(50) was 0.5, 13.7, and 5.7 nM, respectively.
研究了拉替拉韦（raltegravir）和其他 4 种整合酶抑制剂（MK-2048、L870,810、IN2 和 IN5）在原代人巨噬细胞、PBMC 和 C8166 淋巴细胞中的活性，以确定它们在不同的 HIV 感染细胞系统中的相对效力和疗效。拉替拉韦在所有细胞类型中均表现出更好的保护效果；MK-2048、L870,810 和 IN5 在巨噬细胞中表现出很强的抗 HIV-1 活性，而在淋巴细胞中，只有 MK-2048 和 L870,810 表现出与拉替拉韦相当的抑制作用。IN2 是一种在所有细胞系统中均效果不佳的抗 HIV-1 化合物。所有有效的整合酶抑制剂对 X4 和 R5 HIV-1 株均表现出很强的抗病毒活性。总的来说，拉替拉韦、MK-2048、L870,810 和 IN5 在巨噬细胞中的抗 HIV 活性与 PBMC 和 C8166 T 细胞相似或略高：对于 MK-2048，EC50 分别为 0.4、0.9 和 11.5 nM；对于 L870,810，EC50 分别为 1.5、14.3 和 10.6 nM；对于 IN5，EC50 分别为 0.5、13.7 和 5.7 nM。
