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Pyrimidone derivative inhibits simian immunodeficiency virus‐induced apoptosis of CEM x174 cells
Author(s) -
Gao Libo,
Fu Shigan,
Li Hui,
Wang Xiaowei,
Liu Junyi,
Liu Han,
Guo Liyuan,
Liu Xinhua,
Li Mengsen,
McNutt Michael A.,
Li Gang
Publication year - 2009
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2008.11.005
Subject(s) - simian immunodeficiency virus , reverse transcriptase , apoptosis , virology , biology , downregulation and upregulation , microbiology and biotechnology , reverse transcriptase inhibitor , nucleoside reverse transcriptase inhibitor , virus , chemistry , rna , viral load , biochemistry , antiretroviral therapy , gene
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.