Gao Libo, Fu Shigan, Li Hui, Wang Xiaowei, Liu Junyi, Liu Han, Guo Liyuan, Liu Xinhua, Li Mengsen, McNutt Michael A, Li Gang
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100083, PR China.
Cell Biol Int. 2009 Feb;33(2):207-16. doi: 10.1016/j.cellbi.2008.11.005. Epub 2008 Nov 24.
The biochemical effects of 2-(ethoxymethylthio)-9-phenyl-cyclohepta[d]pyrimidone (EPCP), a novel non-nucleoside reverse transcriptase inhibitor, have been investigated. Treatment with EPCP (EC(50) of 0.88 nM in CEM x174 cells) significantly inhibited the activity of SIV reverse transcriptase and elevated the percentage of viable cells in an SIV-infected sample in a dose-dependent manner. The percentage of cells accumulated in G1 phase increased significantly from 34.5 to 62.4%, with a concomitant reduction in S-phase from 50.7% in the control to 22.6% in the infected group. This cell cycle profile was restored by treatment with EPCP. SIV upregulated the levels of the caspase-3, p53 and bax proteins, and downregulated the level of bcl-2 in infected cells. The apoptotic effect of SIV was also blocked by treatment with EPCP. The pharmacological effects of EPCP paralleled those of AZT, suggesting the possibility that EPCP might be a novel antiviral agent for SIV.
对新型非核苷类逆转录酶抑制剂2-（乙氧基甲基硫代）-9-苯基-环庚并[d]嘧啶酮（EPCP）的生化效应进行了研究。用EPCP处理（在CEM x174细胞中的半数有效浓度（EC50）为0.88 nM）可显著抑制SIV逆转录酶的活性，并以剂量依赖的方式提高SIV感染样本中活细胞的百分比。G1期积累的细胞百分比从34.5%显著增加到62.4%，同时S期从对照组的50.7%降至感染组的22.6%。通过用EPCP处理可恢复这种细胞周期分布。SIV上调了感染细胞中caspase-3、p53和bax蛋白的水平，并下调了bcl-2的水平。用EPCP处理也可阻断SIV的凋亡效应。EPCP的药理作用与齐多夫定（AZT）的药理作用相似，这表明EPCP可能是一种新型的抗SIV病毒药物。
