Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity
文献类型：期刊论文
| 作者 | Li, Baoli1; Ni, Shuaishuai1; Mao, Fei1; Chen, Feifei2; Liu, Yifu1; Wei, Hanwen1; Chen, Wenhua1; Zhu, Jin1; Lan, Lefu2 ; Li, Jian1
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2018-01-11 |
| 卷号 | 61期号:1页码:224-250 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.7b01300 |
| 文献子类 | Article |
| 英文摘要 | CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus Newman and 13 MRSA strains (IC50 = 0.02-10.5 nM), along with lower hERG inhibition (IC50 > 30 mu M, similar to 10-fold decrease in comparison with 1). Furthermore, 23a and 23b were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, 23a could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that 23a has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug. |
| WOS关键词 | RESISTANT STAPHYLOCOCCUS-AUREUS ; LINEZOLID RESISTANCE ; VANCOMYCIN-INTERMEDIATE ; VIRULENCE ; MRSA ; EPIDEMIC ; ENTEROCOCCI ; INFECTIONS ; DAPTOMYCIN ; EMERGENCE |
| 资助项目 | National Key R&D Program of China[2017YFB0202600] ; National Natural Science Foundation of China[21672064] ; "Shu Guang" project - Shanghai Municipal Education Commission[00000000] ; "Shu Guang" project - Shanghai Education Development Foundation[14SG28] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000422810800013 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272284]  |
| 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.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Baoli,Ni, Shuaishuai,Mao, Fei,et al. Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity[J]. JOURNAL OF MEDICINAL CHEMISTRY,2018,61(1):224-250. |
| APA | Li, Baoli.,Ni, Shuaishuai.,Mao, Fei.,Chen, Feifei.,Liu, Yifu.,...&Li, Jian.(2018).Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity.JOURNAL OF MEDICINAL CHEMISTRY,61(1),224-250. |
| MLA | Li, Baoli,et al."Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity".JOURNAL OF MEDICINAL CHEMISTRY 61.1(2018):224-250. |
入库方式： OAI收割
来源：上海药物研究所
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