Discovery of Benzocycloalkane Derivatives Efficiently Blocking Bacterial Virulence for the Treatment of Methicillin-Resistant S. aureus (MRSA) Infections by Targeting Diapophytoene Desaturase (CrtN)
文献类型：期刊论文
| 作者 | Wang, Youxin2; Di, Hongxia3; Chen, Feifei3; Xu, Yong1; Xiao, Qiang1; Wang, Xuehai4; Wei, Hanwen2; Lu, Yanli2; Zhang, Lingling2; Zhu, Jin2 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2016-05-26 |
| 卷号 | 59期号:10页码:4831-4848 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.6b00122 |
| 文献子类 | Article |
| 英文摘要 | Antivirulence strategies are now attracting interest for the inherent mechanism of action advantages. In our previous work, diapophytoene desaturase (CrtN) was identified to be an attractive and drugable target for fighting pigmented S. aureus infections. In this research, we developed a series of effective benzocycloalkane-derived CrtN inhibitors with submicromolar IC50. Analogue 8 blocked the pigment biosynthesis of three MRSA strains with a nanomolar IC50 value. Corresponding to its mode of action, 8 did not function as a bactericidal agent. 8 could sensitize S. aureus to immune clearance. In vivo, 8 was proven to be efficacious in an S. aureus Newman sepsis model and abscess formation model. For two typical MRSAs,. USA400 MW2 and Mu50, 8 significantly decreased the staphylococcal loads in the liver and kidneys. Moreover, 8 showed minimal antifungal activity compared to that of NTF. In summary, 8 has the potential to be developed as a therapeutic drug, especially against intractable MRSA issues. |
| WOS关键词 | STAPHYLOCOCCUS-AUREUS ; STAPHYLOXANTHIN ; ANTIVIRULENCE ; BIOSYNTHESIS ; NAFTIFINE ; EPIDEMIC ; PARADIGM |
| 资助项目 | National Natural Science Foundation of China[21222211] ; National Natural Science Foundation of China[21372001] ; National Natural Science Foundation of China[21472207] ; "Shu Guang" project - Shanghai Municipal Education Commission[00000000] ; Shanghai Education Development Foundation[14SG28] ; Program for New Century Excellent Talents in University[NCET-12-0853] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000376840600032 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276034]  |
| 专题 | 药理学第三研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Lan, Lefu; Li, Jian |
| 作者单位 | 1.Hubei Biopharmaceut Ind Technol Inst Inc, Wuhan 430075, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Humanwell Healthcare Grp Co Ltd, Wuhan 430075, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Youxin,Di, Hongxia,Chen, Feifei,et al. Discovery of Benzocycloalkane Derivatives Efficiently Blocking Bacterial Virulence for the Treatment of Methicillin-Resistant S. aureus (MRSA) Infections by Targeting Diapophytoene Desaturase (CrtN)[J]. JOURNAL OF MEDICINAL CHEMISTRY,2016,59(10):4831-4848. |
| APA | Wang, Youxin.,Di, Hongxia.,Chen, Feifei.,Xu, Yong.,Xiao, Qiang.,...&Li, Jian.(2016).Discovery of Benzocycloalkane Derivatives Efficiently Blocking Bacterial Virulence for the Treatment of Methicillin-Resistant S. aureus (MRSA) Infections by Targeting Diapophytoene Desaturase (CrtN).JOURNAL OF MEDICINAL CHEMISTRY,59(10),4831-4848. |
| MLA | Wang, Youxin,et al."Discovery of Benzocycloalkane Derivatives Efficiently Blocking Bacterial Virulence for the Treatment of Methicillin-Resistant S. aureus (MRSA) Infections by Targeting Diapophytoene Desaturase (CrtN)".JOURNAL OF MEDICINAL CHEMISTRY 59.10(2016):4831-4848. |
入库方式： OAI收割
来源：上海药物研究所
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