Pyrimidone derivative inhibits simian immunodeficiency virus-induced apoptosis of CEM x174 cells.
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.
Gao
Libo
L
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100083, PR China.
Fu
Shigan
S
Li
Hui
H
Wang
Xiaowei
X
Liu
Junyi
J
Liu
Han
H
Guo
Liyuan
L
Liu
Xinhua
X
Li
Mengsen
M
McNutt
Michael A
MA
Li
Gang
G
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D018613:Microscopy, Confocal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C539424:2-(ethoxymethylthio)-9-phenylcyclohepta(d)pyrimidone; D019253:Proto-Oncogene Proteins c-bcl-2; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3