Synthesis, spectroscopic characterization, and antibacterial activity of chalcone (2E)-1-(3′-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one against multiresistant Staphylococcus aureus carrier of efflux pump mechanisms and β-lactamase

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Larissa da Silva, Isydório Alves Donato, Suieny Rodrigues Bezerra, Hélcio Silva dos Santos, Paulo Nogueira Bandeira, Maria Thalia Ramos do Nascimento, Jesyka Macêdo Guedes, Priscila Ramos Freitas, Ana Carolina Justino de Araújo, Thiago Sampaio de Freitas, Henrique Douglas Melo Coutinho, Yedda Maria Lobo Soares de Matos, Lígia Cláudia Castro de Oliveira, Francisco Assis Bezerra da Cunha
{"title":"Synthesis, spectroscopic characterization, and antibacterial activity of chalcone (2E)-1-(3′-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one against multiresistant Staphylococcus aureus carrier of efflux pump mechanisms and β-lactamase","authors":"Larissa da Silva,&nbsp;Isydório Alves Donato,&nbsp;Suieny Rodrigues Bezerra,&nbsp;Hélcio Silva dos Santos,&nbsp;Paulo Nogueira Bandeira,&nbsp;Maria Thalia Ramos do Nascimento,&nbsp;Jesyka Macêdo Guedes,&nbsp;Priscila Ramos Freitas,&nbsp;Ana Carolina Justino de Araújo,&nbsp;Thiago Sampaio de Freitas,&nbsp;Henrique Douglas Melo Coutinho,&nbsp;Yedda Maria Lobo Soares de Matos,&nbsp;Lígia Cláudia Castro de Oliveira,&nbsp;Francisco Assis Bezerra da Cunha","doi":"10.1111/fcp.12938","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>The bacterium <i>Staphylococcus</i> aureus has stood out for presenting a high adaptability, acquiring resistance to multiple drugs. The search for natural or synthetic compounds with antibacterial properties capable of reversing the resistance of <i>S. aureus</i> is the main challenge to be overcome today. Natural products such as chalcones are substances present in the secondary metabolism of plants, presenting important biological activities such as antitumor, antidiabetic, and antimicrobial activity.</p>\n </section>\n \n <section>\n \n <h3> Objectives</h3>\n \n <p>In this context, the aim of this work was to synthesize the chalcone (2<i>E</i>)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one with nomenclature CMADMA, confirm its structure by nuclear magnetic resonance (NMR), and evaluate its antibacterial properties.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The synthesis methodology used was that of Claisen-Schmidt, and spectroscopic characterization was performed by NMR. For microbiological assays, the broth microdilution methodology was adopted in order to analyze the antibacterial potential of chalcones and to analyze their ability to act as a possible inhibitor of β-lactamase and efflux pump resistance mechanisms, present in S. aureus strain K4100.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The results obtained show that CMADMA does not show direct antibacterial activity, expressing a MIC of ≥1024 μg/mL, or on the enzymatic mechanism of β-lactamase; however, when associated with ethidium bromide in efflux pump inhibition assays, CMADMA showed promising activity by reducing the MIC of the bromide from 64 to 32 μg/mL.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>We conclude that the chalcone synthesized in this study is a promising substance to combat bacterial resistance, possibly acting in the inhibition of the QacC efflux pump present in <i>S. aureus</i> strain K4100, as evidenced by the reduction in the MIC of ethidium bromide.</p>\n </section>\n </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 1","pages":"60-71"},"PeriodicalIF":2.1000,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fundamental & Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/fcp.12938","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

The bacterium Staphylococcus aureus has stood out for presenting a high adaptability, acquiring resistance to multiple drugs. The search for natural or synthetic compounds with antibacterial properties capable of reversing the resistance of S. aureus is the main challenge to be overcome today. Natural products such as chalcones are substances present in the secondary metabolism of plants, presenting important biological activities such as antitumor, antidiabetic, and antimicrobial activity.

Objectives

In this context, the aim of this work was to synthesize the chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one with nomenclature CMADMA, confirm its structure by nuclear magnetic resonance (NMR), and evaluate its antibacterial properties.

Methods

The synthesis methodology used was that of Claisen-Schmidt, and spectroscopic characterization was performed by NMR. For microbiological assays, the broth microdilution methodology was adopted in order to analyze the antibacterial potential of chalcones and to analyze their ability to act as a possible inhibitor of β-lactamase and efflux pump resistance mechanisms, present in S. aureus strain K4100.

Results

The results obtained show that CMADMA does not show direct antibacterial activity, expressing a MIC of ≥1024 μg/mL, or on the enzymatic mechanism of β-lactamase; however, when associated with ethidium bromide in efflux pump inhibition assays, CMADMA showed promising activity by reducing the MIC of the bromide from 64 to 32 μg/mL.

Conclusion

We conclude that the chalcone synthesized in this study is a promising substance to combat bacterial resistance, possibly acting in the inhibition of the QacC efflux pump present in S. aureus strain K4100, as evidenced by the reduction in the MIC of ethidium bromide.

(2E)-1-(3'-氨基苯基)-3-(4-二甲基氨基苯基)-丙-2-烯-1-酮的合成、光谱表征和对多耐药性金黄色葡萄球菌外排泵机制和β-内酰胺酶载体的抗菌活性。
背景:金黄色葡萄球菌具有很强的适应性,可对多种药物产生抗药性。寻找能逆转金黄色葡萄球菌抗药性的天然或合成抗菌化合物是当今面临的主要挑战。天然产物(如查尔酮)是存在于植物二次代谢中的物质,具有重要的生物活性,如抗肿瘤、抗糖尿病和抗菌活性:在此背景下,本研究旨在合成(2E)-1-(3'-氨基苯基)-3-(4-二甲基氨基苯基)-丙-2-烯-1-酮(命名为 CMADMA),通过核磁共振(NMR)确认其结构,并评估其抗菌特性:方法:采用克莱森-施密特合成方法,并通过核磁共振进行光谱鉴定。在微生物检测方面,采用肉汤微稀释法分析查耳酮的抗菌潜力,并分析其作为金黄色葡萄球菌菌株 K4100 中存在的β-内酰胺酶和外排泵耐药机制的可能抑制剂的能力:结果表明,CMADMA 没有显示出直接的抗菌活性,其 MIC ≥1024 μg/mL,也没有对 β-内酰胺酶的酶学机制产生影响;然而,当与溴化乙锭一起进行外排泵抑制试验时,CMADMA 显示出了良好的活性,将溴化乙锭的 MIC 从 64 μg/mL降至 32 μg/mL:我们得出的结论是,本研究中合成的查尔酮是一种很有希望消除细菌耐药性的物质,其作用可能是抑制金黄色葡萄球菌菌株 K4100 中的 QacC 外排泵,溴化乙锭的 MIC 值降低就证明了这一点。
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
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
×
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