論文 - 詳細
| RRC ID | 6868 |
|---|---|
| 著者 | Iwai Y, Takahashi H, Hatakeyama D, Motoshima K, Ishikawa M, Sugita K, Hashimoto Y, Harada Y, Itamura S, Odagiri T, Tashiro M, Sei Y, Yamaguchi K, Kuzuhara T. |
| タイトル | Anti-influenza activity of phenethylphenylphthalimide analogs derived from thalidomide. |
| ジャーナル | Bioorg Med Chem |
| Abstract |
Swine-origin influenza A virus has caused pandemics throughout the world and influenza A is regarded as a serious global health issue. Hence, novel drugs that will target these viruses are very desirable. Influenza A expresses an RNA polymerase essential for its transcription and replication which comprises PA, PB1, and PB2 subunits. We identified potential novel anti-influenza agents from a screen of 34 synthesized phenethylphenylphthalimide analogs derived from thalidomide (PPT analogs). For this screen we used a PA endonuclease inhibition assay, a PB2 pathogenicity-determinant domain-binding assay, and an anti-influenza A virus assay. Three PPT analogs, PPT-65, PPT-66, and PPT-67, were found to both inhibit PA endonuclease activity and retard the growth of influenza A, suggesting a correlation between their activities. PPT-28 was also found to inhibit the growth of influenza A. These four analogs have a 3,4-dihydroxyphenethyl group in common. We also discuss the possibility that 3,4-dihydroxyphenethyl group flexibility may play an important functional role in PA endonuclease inhibition. Another analog harboring a dimethoxyphenethyl group, PPT-62, showed PB2 pathogenicity-determinant domain-binding activity, but did not inhibit the growth of the virus. Our present results indicate the utility of the PA endonuclease assay in the screening of anti-influenza drugs and are therefore useful for future strategies to develop novel anti-influenza A drugs and for mapping the function of the influenza A RNA polymerase subunits. |
| 巻・号 | 18(14) |
| ページ | 5379-90 |
| 公開日 | 2010-7-15 |
| DOI | 10.1016/j.bmc.2010.05.035 |
| PII | S0968-0896(10)00454-2 |
| PMID | 20538468 |
| MeSH | Animals Antiviral Agents / chemical synthesis Antiviral Agents / chemistry* Antiviral Agents / pharmacology* Cell Line DNA-Directed RNA Polymerases / metabolism Dogs Humans Influenza A virus / drug effects* Influenza A virus / enzymology Influenza, Human / drug therapy* Orthomyxoviridae Infections / drug therapy Phthalimides / chemical synthesis Phthalimides / chemistry Phthalimides / pharmacology Stilbenes / chemical synthesis Stilbenes / chemistry Stilbenes / pharmacology Thalidomide / chemical synthesis Thalidomide / chemistry* Thalidomide / pharmacology* |
| IF | 3.073 |
| 引用数 | 35 |
| WOS 分野 | CHEMISTRY, MEDICINAL CHEMISTRY, ORGANIC BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pBMSA-PA (RDB01971) pBMSA-PB2 (RDB01969). |