作为抗结核药的新型季铵盐吡啶和吲哚利嗪衍生物的合成和结构阐明:硅学和体外筛选

IF 4 2区 化学 Q2 CHEMISTRY, PHYSICAL
{"title":"作为抗结核药的新型季铵盐吡啶和吲哚利嗪衍生物的合成和结构阐明:硅学和体外筛选","authors":"","doi":"10.1016/j.molstruc.2024.139851","DOIUrl":null,"url":null,"abstract":"<div><p>The <em>in vitro</em> anti-mycobacterial activity of a novel series of diversely substituted quaternary pyridinium salts (<strong>3a-m</strong>) and indolizines (<strong>5a-h</strong>) were assessed against H37Rv strain of <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>). The series of intermediate 1-(2-oxo-2-phenylethyl)-4-(piperidin-1-yl)pyridin-1-ium bromide, which contains a heterocyclic ring molecule, has been prepared by reacting with 4-(piperidin-1-yl)pyridine and phenacyl bromide at room temperature. The final ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues were prepared by using pyridin-1-ium bromide with electron-deficient acetylene, undergoing 1, 3-dipolar cycloaddition at the ambient temperature using anhydrous potassium carbonate and N, N-dimethylformamide as a solvent. All the newly synthesized compounds were characterized by spectroscopic techniques such as <sup>1</sup>H and <sup>13</sup>C NMR, and HRMS. All the synthesized intermediates and final compounds were evaluated for their anti-tubercular activities against H37Rv (ATCC 27294) strain. All the compounds exhibited anti-tubercular activities in the range of 12.5–50 µM. <em>In vitro</em> screening of all derivatives concluded that among all the screened candidates <strong>3k</strong> emerged as an active hit with MIC 12.5 µM, <strong>3l</strong> and <strong>3m</strong> with MIC 25 µM.</p></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and structural elucidation of novel quaternary pyridinium salt and indolizine derivatives as an anti-tubercular agent: In Silico and In Vitro screening\",\"authors\":\"\",\"doi\":\"10.1016/j.molstruc.2024.139851\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The <em>in vitro</em> anti-mycobacterial activity of a novel series of diversely substituted quaternary pyridinium salts (<strong>3a-m</strong>) and indolizines (<strong>5a-h</strong>) were assessed against H37Rv strain of <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>). The series of intermediate 1-(2-oxo-2-phenylethyl)-4-(piperidin-1-yl)pyridin-1-ium bromide, which contains a heterocyclic ring molecule, has been prepared by reacting with 4-(piperidin-1-yl)pyridine and phenacyl bromide at room temperature. The final ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues were prepared by using pyridin-1-ium bromide with electron-deficient acetylene, undergoing 1, 3-dipolar cycloaddition at the ambient temperature using anhydrous potassium carbonate and N, N-dimethylformamide as a solvent. All the newly synthesized compounds were characterized by spectroscopic techniques such as <sup>1</sup>H and <sup>13</sup>C NMR, and HRMS. All the synthesized intermediates and final compounds were evaluated for their anti-tubercular activities against H37Rv (ATCC 27294) strain. All the compounds exhibited anti-tubercular activities in the range of 12.5–50 µM. <em>In vitro</em> screening of all derivatives concluded that among all the screened candidates <strong>3k</strong> emerged as an active hit with MIC 12.5 µM, <strong>3l</strong> and <strong>3m</strong> with MIC 25 µM.</p></div>\",\"PeriodicalId\":16414,\"journal\":{\"name\":\"Journal of Molecular Structure\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Structure\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022286024023603\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Structure","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022286024023603","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0

摘要

针对结核分枝杆菌(M.tb)H37Rv 株,评估了一系列新型多元取代的季铵盐吡啶(3a-m)和吲哚利嗪(5a-h)的体外抗分枝杆菌活性。一系列含有杂环分子的中间体 1-(2-氧代-2-苯基乙基)-4-(哌啶-1-基)吡啶-1-鎓溴化物是在室温下与 4-(哌啶-1-基)吡啶和苯乙酰溴反应制备的。最终的 3-苯甲酰基-7-(哌啶-1-基)吲嗪-1-甲酸乙酯类似物是用溴化吡啶-1-鎓与缺电子的乙炔,在常温下以无水碳酸钾和 N,N-二甲基甲酰胺为溶剂进行 1,3-二极环化反应制备的。所有新合成的化合物都通过 1H 和 13C NMR 以及 HRMS 等光谱技术进行了表征。评估了所有合成的中间体和最终化合物对 H37Rv(ATCC 27294)菌株的抗结核活性。所有化合物的抗结核活性都在 12.5-50 µM 之间。对所有衍生物进行体外筛选后得出的结论是,在所有筛选出的候选化合物中,3k 是一个有活性的化合物,其 MIC 为 12.5 µM,3l 和 3m 的 MIC 为 25 µM。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and structural elucidation of novel quaternary pyridinium salt and indolizine derivatives as an anti-tubercular agent: In Silico and In Vitro screening

The in vitro anti-mycobacterial activity of a novel series of diversely substituted quaternary pyridinium salts (3a-m) and indolizines (5a-h) were assessed against H37Rv strain of Mycobacterium tuberculosis (M.tb). The series of intermediate 1-(2-oxo-2-phenylethyl)-4-(piperidin-1-yl)pyridin-1-ium bromide, which contains a heterocyclic ring molecule, has been prepared by reacting with 4-(piperidin-1-yl)pyridine and phenacyl bromide at room temperature. The final ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues were prepared by using pyridin-1-ium bromide with electron-deficient acetylene, undergoing 1, 3-dipolar cycloaddition at the ambient temperature using anhydrous potassium carbonate and N, N-dimethylformamide as a solvent. All the newly synthesized compounds were characterized by spectroscopic techniques such as 1H and 13C NMR, and HRMS. All the synthesized intermediates and final compounds were evaluated for their anti-tubercular activities against H37Rv (ATCC 27294) strain. All the compounds exhibited anti-tubercular activities in the range of 12.5–50 µM. In vitro screening of all derivatives concluded that among all the screened candidates 3k emerged as an active hit with MIC 12.5 µM, 3l and 3m with MIC 25 µM.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Molecular Structure
Journal of Molecular Structure 化学-物理化学
CiteScore
7.10
自引率
15.80%
发文量
2384
审稿时长
45 days
期刊介绍: The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信