• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

新型杂环截短侧耳素衍生物的合成及生物活性评价

Synthesis and Biological Activity Evaluation of Novel Heterocyclic Pleuromutilin Derivatives.

作者信息

Yi Yunpeng, Fu Yunxing, Dong Pengcheng, Qin Wenwen, Liu Yu, Liang Jiangping, Shang Ruofeng

机构信息

Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China.

出版信息

Molecules. 2017 Jun 15;22(6):996. doi: 10.3390/molecules22060996.

DOI:10.3390/molecules22060996
PMID:28617344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6152684/
Abstract

A series of pleuromutilin derivatives were synthesized by two synthetic procedures under mild reaction conditions and characterized by Nuclear Magnetic Resonance (NMR), Infrared Spectroscopy (IR), and High Resolution Mass Spectrometer (HRMS). Most of the derivatives with heterocyclic groups at the C-14 side of pleuromutilin exhibited excellent in vitro antibacterial activities against , methicillin-resistant (MRSA), methicillin-resistant (MRSE), and vancomycin-resistant (VRE) in vitro antibacterial activity. The synthesized derivatives which contained pyrimidine rings, , , and , displayed modest antibacterial activities. Compound , the most active antibacterial agent, displayed rapid bactericidal activity and affected bacterial growth in the same manner as that of tiamulin fumarate. Moreover, molecular docking studies of and lefamulin provided similar information about the interactions between the compounds and 50S ribosomal subunit. The results of the study show that pyrimidine rings should be considered in the drug design of pleuromutilin derivatives.

摘要

通过两种合成方法在温和反应条件下合成了一系列截短侧耳素衍生物，并通过核磁共振（NMR）、红外光谱（IR）和高分辨率质谱仪（HRMS）对其进行了表征。大多数在截短侧耳素C-14侧带有杂环基团的衍生物对耐甲氧西林金黄色葡萄球菌（MRSA）、耐甲氧西林表皮葡萄球菌（MRSE）和耐万古霉素肠球菌（VRE）表现出优异的体外抗菌活性。含有嘧啶环、[此处原文缺失具体化合物]、[此处原文缺失具体化合物]和[此处原文缺失具体化合物]的合成衍生物表现出适度的抗菌活性。活性最强的抗菌剂化合物[此处原文缺失具体化合物]表现出快速杀菌活性，并且以与延胡索酸泰妙菌素相同的方式影响细菌生长。此外，[此处原文缺失具体化合物]和莱伐米星的分子对接研究提供了有关这些化合物与50S核糖体亚基之间相互作用的类似信息。研究结果表明，在截短侧耳素衍生物的药物设计中应考虑嘧啶环。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/e50e0344217f/molecules-22-00996-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/cf34daecfb67/molecules-22-00996-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/2e5b370ba1be/molecules-22-00996-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/e8c3a84d2f37/molecules-22-00996-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/5586d721e842/molecules-22-00996-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/bfdee0919853/molecules-22-00996-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/e50e0344217f/molecules-22-00996-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/cf34daecfb67/molecules-22-00996-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/2e5b370ba1be/molecules-22-00996-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/e8c3a84d2f37/molecules-22-00996-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/5586d721e842/molecules-22-00996-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/bfdee0919853/molecules-22-00996-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d3/6152684/e50e0344217f/molecules-22-00996-g004.jpg

相似文献

1
Synthesis and Biological Activity Evaluation of Novel Heterocyclic Pleuromutilin Derivatives.新型杂环截短侧耳素衍生物的合成及生物活性评价
Molecules. 2017 Jun 15;22(6):996. doi: 10.3390/molecules22060996.
2
Synthesis and antibacterial activities of novel pleuromutilin derivatives with a substituted pyrimidine moiety.具有取代嘧啶部分的新型截短侧耳素衍生物的合成及抗菌活性
Eur J Med Chem. 2017 Jan 27;126:687-695. doi: 10.1016/j.ejmech.2016.11.054. Epub 2016 Nov 30.
3
Synthesis and Antibacterial Activity Against MRSA of Pleuromutilin Derivatives Possessing a Mercaptoethylamine Linker.具有巯基乙胺连接基的截短侧耳素衍生物的合成及其对耐甲氧西林金黄色葡萄球菌的抗菌活性
Med Chem. 2018;14(6):585-594. doi: 10.2174/1573406414666180416131737.
4
Synthesis and evaluation of novel pleuromutilin derivatives with a substituted pyrimidine moiety.含取代嘧啶部分的新型截短侧耳素衍生物的合成与评价
Eur J Med Chem. 2015 Aug 28;101:179-84. doi: 10.1016/j.ejmech.2015.06.034. Epub 2015 Jun 22.
5
Design, synthesis, and biological activity evaluation of a series of pleuromutilin derivatives with novel C14 side chains.设计、合成及新型 C14 侧链的截短侧耳素衍生物的生物活性评价。
Bioorg Med Chem Lett. 2020 Apr 1;30(7):126969. doi: 10.1016/j.bmcl.2020.126969. Epub 2020 Jan 18.
6
Design, synthesis and antibacterial evaluation of novel pleuromutilin derivatives possessing piperazine linker.新型含哌嗪连接基的截短侧耳素衍生物的设计、合成与抗菌活性评价。
Eur J Med Chem. 2017 Feb 15;127:286-295. doi: 10.1016/j.ejmech.2017.01.004. Epub 2017 Jan 3.
7
Synthesis and Pharmacological Evaluation of Novel Pleuromutilin Derivatives with Substituted Benzimidazole Moieties.含取代苯并咪唑部分的新型截短侧耳素衍生物的合成与药理评价
Molecules. 2016 Nov 8;21(11):1488. doi: 10.3390/molecules21111488.
8
Discovery of novel pleuromutilin derivatives as potent antibacterial agents.新型截短侧耳素衍生物的发现及其作为强效抗菌剂的潜力。
Eur J Med Chem. 2022 Jul 5;237:114403. doi: 10.1016/j.ejmech.2022.114403. Epub 2022 Apr 20.
9
Novel pleuromutilin derivatives as antibacterial agents: synthesis, biological evaluation and molecular docking studies.新型截短侧耳素衍生物作为抗菌剂：合成、生物评价和分子对接研究。
Bioorg Med Chem Lett. 2012 Oct 1;22(19):6166-72. doi: 10.1016/j.bmcl.2012.08.021. Epub 2012 Aug 10.
10
Synthesis and antibacterial activities of novel pleuromutilin derivatives bearing an aminothiophenol moiety.新型含氨巯基苯酚片段的截短侧耳素衍生物的合成与抗菌活性。
Chem Biol Drug Des. 2018 Sep;92(3):1627-1637. doi: 10.1111/cbdd.13328. Epub 2018 May 31.

引用本文的文献

1
Navigating Antibacterial Frontiers: A Panoramic Exploration of Antibacterial Landscapes, Resistance Mechanisms, and Emerging Therapeutic Strategies.探索抗菌前沿：全景式探索抗菌领域、耐药机制及新兴治疗策略。
ACS Infect Dis. 2024 May 10;10(5):1483-1519. doi: 10.1021/acsinfecdis.4c00115. Epub 2024 May 1.
2
Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure-Activity Relationship Model.利用定量构效关系模型设计和合成截短侧耳素衍生物作为抗菌剂。
Int J Mol Sci. 2024 Feb 13;25(4):2256. doi: 10.3390/ijms25042256.
3
Treatment of MRSA Infection: Where are We?

本文引用的文献

1
What is an "ideal" antibiotic? Discovery challenges and path forward.什么是“理想”的抗生素？发现的挑战和前进的道路。
Biochem Pharmacol. 2017 Jun 1;133:63-73. doi: 10.1016/j.bcp.2017.01.003. Epub 2017 Jan 10.
2
A novel pleuromutilin antibacterial compound, its binding mode and selectivity mechanism.一种新型截短侧耳素类抗菌化合物，其结合模式和选择性机制。
Sci Rep. 2016 Dec 13;6:39004. doi: 10.1038/srep39004.
3
Synthesis and Pharmacological Evaluation of Novel Pleuromutilin Derivatives with Substituted Benzimidazole Moieties.含取代苯并咪唑部分的新型截短侧耳素衍生物的合成与药理评价
耐甲氧西林金黄色葡萄球菌感染的治疗：我们在哪里？
Curr Med Chem. 2024;31(28):4425-4460. doi: 10.2174/0109298673249381231130111352.
4
Three-Dimensional Structure and Optimization of the Metallo-β-Lactamase Inhibitor Aspergillomarasmine A.金属β-内酰胺酶抑制剂曲霉茉莉素A的三维结构与优化
ACS Omega. 2022 Jan 26;7(5):4170-4184. doi: 10.1021/acsomega.1c05757. eCollection 2022 Feb 8.
5
Synthesis, Antibacterial and Pharmacokinetic Evaluation of Novel Derivatives of Harmine N-Cinnamic Acid.新型哈尔满 N-肉桂酸衍生物的合成、抗菌活性及药代动力学评价。
Molecules. 2021 Aug 10;26(16):4842. doi: 10.3390/molecules26164842.
6
Development of Indirect Competitive Enzyme-Linked Immunosorbent and Immunochromatographic Strip Assays for Tiamulin Detection in Chicken.鸡中泰妙菌素检测的间接竞争酶联免疫吸附测定法和免疫层析试纸条测定法的开发
ACS Omega. 2018 Mar 28;3(3):3581-3586. doi: 10.1021/acsomega.8b00289. eCollection 2018 Mar 31.
7
Introduction: lefamulin and pharmacokinetic/pharmacodynamic rationale to support the dose selection of lefamulin.简介：来氟米特和药代动力学/药效学原理支持来氟米特的剂量选择。
J Antimicrob Chemother. 2019 Apr 1;74(Suppl 3):iii2-iii4. doi: 10.1093/jac/dkz084.
Molecules. 2016 Nov 8;21(11):1488. doi: 10.3390/molecules21111488.
4
Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm.含C(5)三唑臂的新型螺旋霉素类似物的合成、抗菌及抗癌活性评价
J Med Chem. 2016 Sep 8;59(17):7963-73. doi: 10.1021/acs.jmedchem.6b00764. Epub 2016 Aug 19.
5
16-Membered Macrolide Lactone Derivatives Bearing a Triazole-Functionalized Arm at the Aglycone C13 Position as Antibacterial and Anticancer Agents.16-元大环内酯内酯类衍生物在糖基 C13 位带有三唑功能化臂，作为抗菌和抗癌药物。
ChemMedChem. 2016 Sep 6;11(17):1886-91. doi: 10.1002/cmdc.201600250. Epub 2016 Jul 14.
6
Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus.对病原菌金黄色葡萄球菌核糖体物种特异性特征的结构洞察。
Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):E5805-14. doi: 10.1073/pnas.1517952112. Epub 2015 Oct 13.
7
Avogadro: an advanced semantic chemical editor, visualization, and analysis platform.阿伏伽德罗：一个先进的语义化学编辑器、可视化和分析平台。
J Cheminform. 2012 Aug 13;4(1):17. doi: 10.1186/1758-2946-4-17.
8
On the specificity of antibiotics targeting the large ribosomal subunit.抗生素靶向大亚基的特异性。
Ann N Y Acad Sci. 2011 Dec;1241:1-16. doi: 10.1111/j.1749-6632.2011.06192.x.
9
The pleuromutilin antibiotics: a new class for human use.截短侧耳素类抗生素：一类供人类使用的新型抗生素。
Curr Opin Investig Drugs. 2010 Feb;11(2):182-91.
10
Similarity based docking.基于相似性的对接。
J Chem Inf Model. 2008 Jan;48(1):186-96. doi: 10.1021/ci700124r. Epub 2007 Nov 29.