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Cell Biology International (2009) 33, 207–216 (Printed in Great Britain)

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Pyrimidone derivative inhibits simian immunodeficiency virus-induced apoptosis of CEM x174 cells

Libo Gao^a1, Shigan Fu^b1, Hui Li^a, Xiaowei Wang^c, Junyi Liu^c, Han Liu^a, Liyuan Guo^a, Xinhua Liu^a, Mengsen Li^a, Michael A. McNutt^d and Gang Li^a*

^aDepartment of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100083, PR China
^bDepartment of Pathophysiology, Hainan Medical Collage, Haikou 570102, PR China
^cDepartment of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China
^dDepartment of Pathology, Peking University Health Science Center, Beijing 100083, PR China

Abstract

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 (EC50 of 0.88nM 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.

Key words: Apoptosis, Cell cycle, Pyrimidone, Reverse transcriptase, Simian immunodeficiency virus.

¹Libo Gao and Shigan Fu contributed equally to this study.

^*Corresponding author. Tel./fax: +86 10 82802891.

Received 14 April 2008/17 July 2008; accepted 12 November 2008