(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。

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2023-07-27 DOI:10.1111/fcp.12938

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

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引用次数: 0

摘要

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。

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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

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.

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

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.