Experimental and Computational Insights into Bis-indolylmethane Derivatives as Potent Antimicrobial Agents Inhibiting 2,2-dialkylglycine Decarboxylase

Q4 Pharmacology, Toxicology and Pharmaceutics
Dnyaneshwar T. Nagre, B. Thorat, Suraj N. Mali, M. Farooqui, B. Agrawal
{"title":"Experimental and Computational Insights into Bis-indolylmethane Derivatives as Potent Antimicrobial Agents Inhibiting 2,2-dialkylglycine Decarboxylase","authors":"Dnyaneshwar T. Nagre, B. Thorat, Suraj N. Mali, M. Farooqui, B. Agrawal","doi":"10.2174/1573408017666210914105731","DOIUrl":null,"url":null,"abstract":"\n\nA series of bis(indolyl)methanes (3a-3o) have been synthesized using a greener and new approach using the reaction of different substituted aldehydes and indole in the presence of an easily available and biodegradable base such as piperidine in acetic acid at room temperature and characterized with UV (Ultraviolet-visible spectroscopy), Gas chromatography-mass spectrometry (GC-MS), Proton nuclear magnetic resonance (H-NMR), and Fourier transform infrared spectroscopy (FTIR). \n\n\n\n\nAll 15 newly synthesized compounds (3a-3o) were subjected to in-vitro anti-microbial activity determination and compared with the known standard drug ciprofloxacin (1-2 µg/mL). Our in-silico analysis on the target protein, pdb id: 1d7u suggested that these analogues would be highly active against bacterial targets and thus, would act as good antimicrobial agents. \n\n\n\n\nAll 15 newly synthesized compounds (3a-3o) displayed potent activity on various experimental microbial strains (1.0-1.4 µg/mL). Compound, 3k was obtained as the best docked compound against common bacterial target enzyme, (pdb id:1d7u). The standard, Ciprofloxacin, retained the docking score of -111.3 Kcal/mol with similar binding amino acid residues (LYS272 (Pi-cation); ALA A:245 (Pi-sigma); TRP A:138 (Pi-Pi); ALA A:112; and MET A:141 (Pi-alkyl)) as of inbound.\n\n\n\n\nWe believe that our current study would shed more light on the development of potent bis(indolyl)methanes as antimicrobial agents.\n\n","PeriodicalId":35405,"journal":{"name":"Current Enzyme Inhibition","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2021-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Enzyme Inhibition","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1573408017666210914105731","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 2

Abstract

A series of bis(indolyl)methanes (3a-3o) have been synthesized using a greener and new approach using the reaction of different substituted aldehydes and indole in the presence of an easily available and biodegradable base such as piperidine in acetic acid at room temperature and characterized with UV (Ultraviolet-visible spectroscopy), Gas chromatography-mass spectrometry (GC-MS), Proton nuclear magnetic resonance (H-NMR), and Fourier transform infrared spectroscopy (FTIR). All 15 newly synthesized compounds (3a-3o) were subjected to in-vitro anti-microbial activity determination and compared with the known standard drug ciprofloxacin (1-2 µg/mL). Our in-silico analysis on the target protein, pdb id: 1d7u suggested that these analogues would be highly active against bacterial targets and thus, would act as good antimicrobial agents. All 15 newly synthesized compounds (3a-3o) displayed potent activity on various experimental microbial strains (1.0-1.4 µg/mL). Compound, 3k was obtained as the best docked compound against common bacterial target enzyme, (pdb id:1d7u). The standard, Ciprofloxacin, retained the docking score of -111.3 Kcal/mol with similar binding amino acid residues (LYS272 (Pi-cation); ALA A:245 (Pi-sigma); TRP A:138 (Pi-Pi); ALA A:112; and MET A:141 (Pi-alkyl)) as of inbound. We believe that our current study would shed more light on the development of potent bis(indolyl)methanes as antimicrobial agents.
双吲哚甲烷衍生物抑制2,2-二烷基甘氨酸脱羧酶的实验和计算研究
以吲哚为原料,在醋酸中以易获得且可生物降解的碱(如哌啶)为溶剂,在室温下,以不同取代醛和吲哚为原料,合成了一系列双吲哚基甲烷(3a- 30),并用紫外可见光谱(UV)、气相色谱-质谱(GC-MS)、质子核磁共振(H-NMR)和傅里叶变换红外光谱(FTIR)对其进行了表征。对新合成的15个化合物(3a- 30)进行体外抑菌活性测定,并与已知标准药物环丙沙星(1-2µg/mL)进行比较。我们对目标蛋白pdb: 1d7u的计算机分析表明,这些类似物对细菌目标具有高度活性,因此可以作为良好的抗菌剂。所有15个新合成的化合物(3a- 30)对不同的实验微生物菌株(1.0 ~ 1.4µg/mL)均表现出较强的活性。化合物3k是抗常见细菌靶酶(pdb id:1d7u)的最佳对接物。标准品环丙沙星与相似的结合氨基酸残基(LYS272 (pi -阳离子))保持-111.3 Kcal/mol的对接分数;ALA A:245 (Pi-sigma);TRP A:138 (Pi-Pi);阿拉巴马州:112;和MET A:141 (pi -烷基))我们相信,我们目前的研究将为开发有效的吲哚基甲烷作为抗菌药物提供更多的线索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Current Enzyme Inhibition
Current Enzyme Inhibition Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
1.30
自引率
0.00%
发文量
30
期刊介绍: Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
×
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