| Title | Inhibitory activity of 9-phenylcyclohepta[d] pyrimidinedione derivatives against different strains of HIV-1 as non-nucleoside reverse transcriptase inhibitors |
| Authors | Huang, Yang Wang, Xiaowei Yu, Xiaoling Yuan, Lin Guo, Ying Xu, Weisi Liu, Tiejun Liu, Junyi Shao, Yiming Ma, Liying |
| Affiliation | Chinese Ctr Dis Control & Prevent CDC, Natl Ctr AIDS STD Control & Prevent NCAIDS, State Key Lab Infect Dis Prevent & Control, Kunming, Peoples R China. Peking Univ, Dept Chem Biol, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China. |
| Keywords | ANTIVIRAL ACTIVITY CHINA |
| Issue Date | 2011 |
| Publisher | virology journal |
| Citation | VIROLOGY JOURNAL.2011,8. |
| Abstract | Background: The non-nucleoside reverse transcriptase inhibitor (NNRTI), as a major component of the highly active antiretroviral therapy (HAART) to HIV-1 (human immunodeficiency virus type 1) infected patients, required the development of new NNRTIs with improved resistance profile and decreased toxicity. Therefore, a series of novel compounds, 9-phenylcyclohepta[d]pyrimidinedione derivatives (PCPs), were designed based on the chemical structure of TNK-651, to detect anti-HIV-1 activity. Results: 1-[(benzyloxy)methyl]-9-phenyl-cyclohepta[d] pyrimidinedione (BmPCP) among four PCPs has antiviral activity on laboratory-adapted HIV strains (HIV-1 SF33). The results showed 50% inhibition concentrations (IC(50)s) of BmPCP were 0.34 mu M, 1.72 mu M and 1.96 mu M on TZM-bl, peripheral blood mononuclear cells (PBMCs) and MT4, respectively. It was also effective against infection by the predominant HIV-1 isolates in China, with IC50s at low mu M levels. Its selectivity index (SI) ranged from 67 to 266 in different cells. The results of time-of-addition assay demonstrated that BmPCP inhibited HIV-1 infection by targeting the post entry of the HIV-1 replication cycle. For inhibition of HIV-1 reverse transcriptase activity, the IC(50) values of BmPCP and NVP were 1.51 and 3.67 mu M, respectively. Conclusions: BmPCP with a novel structure acts as a NNRTI to inhibit HIV-1 replication and can serve as a lead compound for further development of new anti-HIV-1 drugs. |
| URI | http://hdl.handle.net/20.500.11897/239701 |
| ISSN | 1743-422X |
| DOI | 10.1186/1743-422X-8-230 |
| Indexed | SCI(E) |
| Appears in Collections: | å å¦ä¸ å å å·¥ç¨ å¦é ¢ 天然药物与仿生药物国家重点实验室 |
