WEKO3
アイテム
Identification of Novel Compounds with Anti-Mycobacterial Activity Using in Silico Screening and Pharmacophore Modeling Targeting Mycobacterium Thymidine Monophosphate Kinase
https://doi.org/10.18997/00004236
https://doi.org/10.18997/0000423646e8b7f8-3c89-4970-98cb-195bcaa4b39a
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
jou_k_298.pdf (8.4 MB)
|
|
| Item type | 学位論文 = Thesis or Dissertation(1) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2015-08-05 | |||||||||
| 資源タイプ | ||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
| 資源タイプ | doctoral thesis | |||||||||
| タイトル | ||||||||||
| タイトル | Identification of Novel Compounds with Anti-Mycobacterial Activity Using in Silico Screening and Pharmacophore Modeling Targeting Mycobacterium Thymidine Monophosphate Kinase | |||||||||
| 言語 | ja | |||||||||
| 言語 | ||||||||||
| 言語 | jpn | |||||||||
| 著者 |
小関, 祐司
× 小関, 祐司
|
|||||||||
| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | The increasing prevalence of drug-resistant tuberculosis （TB）, which is resistant to effective multiple antibiotic, remains a major public health menace. The Mycobacterium tuberculosis （M. tuberculosis） thymidine monophosphate kinase （mtTMPK）, which is an essential enzyme for the maintenance of the thymidine triphosphate pools, is considered a potential enzymatic target for the development of effective antibiotics against TB. In this study, I attempted to identify novel compounds with anti-mycobacterial activity specifically targeting mtTMPK. I performed in silico structure-based drug screening （SBDS） with a large-scale virtual compound library （6,192,932 compounds） and phramacophore-based in silico screening with a compound library of 461,383 compounds. I then evaluated the inhibitory effects of candidate compounds on model mycobacteria strains. As a result, I found that compounds K10, KTP3, KTPS1, and KTPS2, completely inhibited the growth of Mycobacterium vanbaalenii （M. vanbaalenii） and/or Mycobacterium smegmatis （M. smegmatis）. In addition, I experimentally demonstrated that two compounds （KTPS1 and KTPS2） directly inhibitedmtTMPK catalytic activity to some extent. Moreover, the most potent chemical compounds, KTPS1, did not exhibit any significant toxic effects on the growth of model intestinal bacteria （Escheichila coli: E. coli） and several mammalian cells. The structural and experimental information regarding these chemical compounds is likely useful for the development of novel antibiotics for the treatment of TB. | |||||||||
| 目次 | ||||||||||
| 内容記述タイプ | TableOfContents | |||||||||
| 内容記述 | 1. Introduction||2. Results||3. Discussion||4. Conclusion||5. Materials and methods | |||||||||
| 備考 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 九州工業大学博士学位論文 学位記番号:情工博甲第298号 学位授与年月日:平成27年3月25日 | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | In silico drug screening | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Molecular Dynamics | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Mycobacterium | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Pharmacophore Modeling | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | TMPK | |||||||||
| アドバイザー | ||||||||||
| 青木, 俊介 | ||||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第298号 | |||||||||
| 学位名 | ||||||||||
| 学位名 | 博士（情報工学） | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2015-03-25 | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||
| 学位授与機関識別子 | 17104 | |||||||||
| 学位授与機関名 | 九州工業大学 | |||||||||
| 学位授与年度 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 平成26年度 | |||||||||
| 出版タイプ | ||||||||||
| 出版タイプ | VoR | |||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
| アクセス権 | ||||||||||
| アクセス権 | open access | |||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
| ID登録 | ||||||||||
| ID登録 | 10.18997/00004236 | |||||||||
| ID登録タイプ | JaLC | |||||||||
