Extra Sugar on Vancomycin: New Analogues for Combating Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci
文献类型：期刊论文
| 作者 | Guan, Dongliang1,2; Chen, Feifei2; Xiong, Lun2,5; Tang, Feng1,2; Faridoon2; Qu, Yunguang1,2; Zhang, Naixia1,2 ; Gong, Likun1,2; Li, Jian5; Lan, Lefu1,2,3
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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:286-304 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.7b01345 |
| 文献子类 | Article |
| 英文摘要 | Lipophilic substitution on vancomycin is an effective strategy for the development of novel vancomycin analogues against drug-resistant bacteria by enhancing bacterial cell wall interactions. However, hydrophobic structures usually lead to long elimination half-life and accumulative toxicity; therefore, hydrophilic fragments were also introduced to the lipo-vancomycin to regulate their pharmacokinetic/pharmacodynamic properties. Here, we synthesized a series of new vancomycin analogues carrying various sugar moieties on the seventh-amino acid phenyl ring and lipophilic substitutions on vancosamine with extensive structure activity relationship analysis. The optimal analogues indicated 128-1024-fold higher activity against methicillin-susceptible S. aureus, vancomycin-intermediate resistant S. aureus (VISA), and vancomycin-resistant Enterococci (VRE) compared with that of vancomycin. In-vivo pharmacokinetics studies demonstrated the effective regulation of extra sugar motifs, which shortened the half-life and addressed concerns of accumulative toxicity of lipo-vancomycin. This work presents an effective strategy for lipo-vancomycin derivative design by introducing extra sugars, which leads to better antibiotic-like properties of enhanced efficacy, optimal pharmacokinetics, and lower toxicity. |
| WOS关键词 | GRAM-POSITIVE INFECTIONS ; GLYCOPEPTIDE ANTIBIOTICS ; REDUCED SUSCEPTIBILITY ; METHICILLIN-RESISTANT ; TETRAZOLIUM SALT ; CELL VIABILITY ; INTERMEDIATE ; TELAVANCIN ; BACTERIA ; LIPOGLYCOPEPTIDES |
| 资助项目 | National Natural Science Foundation of China (NNSFC)[21372238] ; National Natural Science Foundation of China (NNSFC)[21572244] ; SIMM institute fund[CASIMM0120162014] ; SIMM institute fund[CASIMM0120164007] ; Youth Innovation Promotion Association of CAS[2017328] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000422810800016 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272285]  |
| 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 生物技术药物研发中心（筹） 药物安全性评价中心 |
| 通讯作者 | Lan, Lefu; Huang, Wei |
| 作者单位 | 1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 2.Chinese Acad Sci, CAS Key Lab Receptor Res, CAS Ctr Excellence Mol Cell Sci, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Ctr Biodrug Dev, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 5.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guan, Dongliang,Chen, Feifei,Xiong, Lun,et al. Extra Sugar on Vancomycin: New Analogues for Combating Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci[J]. JOURNAL OF MEDICINAL CHEMISTRY,2018,61(1):286-304. |
| APA | Guan, Dongliang.,Chen, Feifei.,Xiong, Lun.,Tang, Feng.,Faridoon.,...&Huang, Wei.(2018).Extra Sugar on Vancomycin: New Analogues for Combating Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci.JOURNAL OF MEDICINAL CHEMISTRY,61(1),286-304. |
| MLA | Guan, Dongliang,et al."Extra Sugar on Vancomycin: New Analogues for Combating Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci".JOURNAL OF MEDICINAL CHEMISTRY 61.1(2018):286-304. |
入库方式： OAI收割
来源：上海药物研究所
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