3-Acylated tetramic and tetronic acids as natural metal binders: myth or reality?

Zaghouani, Mehdi; Nay, Bastien

doi:10.1039/c5np00144g

Cited by 39 publications

(39 citation statements)

References 103 publications

(61 reference statements)

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“…The tautomerization of tetramic acids is essential to their bioactivity and metal binding activities and has been studied in detail [40,41]. For example, the pKa of tetramic acids is~2.5-4 [16]. Thus, we hypothesize that in tetramic acids, the pyrrolidinedione warhead could bind in the same place as in the moiramide B series.…”

Section: Plos Onementioning

confidence: 95%

“…However, one transcription process noted as a possible indicator of PYRC mechanism of action was cation binding, more specifically metal ion binding. Metal binding has been suggested as an important feature of EQI bioactivity [14][15][16].…”

Section: Plos Onementioning

confidence: 99%

“…Based upon the published data and transcriptome indicators, we explored metal homeostasis in EQI treated S. aureus. Tetramic acids are known to bind metal ions [16]. Upon proton loss, the tetramate anion has several resonance forms that promote bidentate interactions with metals [15].…”

Section: Eqi Antibacterial Activity Not Affected By Metal Ion Concentmentioning

confidence: 99%

“…Moiramide B and andrimid are 2,5-pyrrolidinedione-based natural products. It was shown that a beta-ketoamide / pyrrolidinedione was essential for activity; the beta-ketoamide was present in the enol tautomer, which bound in the same place that anion chemistry would take place during the catalytic cycle [14][15][16]. Similarly, tetramic acids are 2,4-pyrrolidinediones, with beta-ketoamides.…”

Section: Plos Onementioning

confidence: 99%

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Pyrrolocin C and equisetin inhibit bacterial acetyl-CoA carboxylase

et al. 2020

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Antimicrobial resistance is a growing global health and economic concern. Current antimicrobial agents are becoming less effective against common bacterial infections. We previously identified pyrrolocins A and C, which showed activity against a variety of Grampositive bacteria. Structurally similar compounds, known as pyrrolidinediones (e.g., TA-289, equisetin), also display antibacterial activity. However, the mechanism of action of these compounds against bacteria was undetermined. Here, we show that pyrrolocin C and equisetin inhibit bacterial acetyl-CoA carboxylase (ACC), the first step in fatty acid synthesis. We used transcriptomic data, metabolomic analysis, fatty acid rescue and acetate incorporation experiments to show that a major mechanism of action of the pyrrolidinediones is inhibition of fatty acid biosynthesis, identifying ACC as the probable molecular target. This hypothesis was further supported using purified proteins, demonstrating that biotin carboxylase is the inhibited component of ACC. There are few known antibiotics that target this pathway and, therefore, we believe that these compounds may provide the basis for alternatives to current antimicrobial therapy.

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Section: Plos Onementioning

confidence: 95%

Section: Plos Onementioning

confidence: 99%

Section: Eqi Antibacterial Activity Not Affected By Metal Ion Concentmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

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Pyrrolocin C and equisetin inhibit bacterial acetyl-CoA carboxylase

et al. 2020

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“…The 3-acyl substituted tetramic rings provide metal binding capacity [22, 23], and this system has been primarily investigated in the fungal metabolite tenuazonic acid which has shown to form complexes with Ca(II) and Mg(II) [24]. Recently, the naturally occurring “chaunolidines A–C” tetramic acid analogues, isolated from an Australian marine-derived fungus, were shown to form metal chelates with Fe(III), Au(II), Cu(II), Mg(II), and Zn(II) [25].…”

Section: Introductionmentioning

confidence: 99%

X-Ray Crystallographic Analysis, EPR Studies, and Computational Calculations of a Cu(II) Tetramic Acid Complex

Matiadis

Tsironis

Stefanou

et al. 2017

Bioinorganic Chemistry and Applications

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In this work we present a structural and spectroscopic analysis of a copper(II) N-acetyl-5-arylidene tetramic acid by using both experimental and computational techniques. The crystal structure of the Cu(II) complex was determined by single crystal X-ray diffraction and shows that the copper ion lies on a centre of symmetry, with each ligand ion coordinated to two copper ions, forming a 2D sheet. Moreover, the EPR spectroscopic properties of the Cu(II) tetramic acid complex were also explored and discussed. Finally, a computational approach was performed in order to obtain a detailed and precise insight of product structures and properties. It is hoped that this study can enrich the field of functional supramolecular systems, giving place to the formation of coordination-driven self-assembly architectures.

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Chemische und biologische Aspekte von “Nutritional Immunity” – Perspektiven für neue Antiinfektiva mit Fokus auf bakterielle Eisenaufnahmesysteme

et al. 2017

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Eine der Verteidigungsstrategien eines Wirtes gegen bakterielle Infektionen ist der Entzug essentieller Metallionen, insbesondere von Eisenionen, durch Komplexierung. Dies wird als Nährstoffimmunität (“nutritional immunity”) bezeichnet. Bakterien haben jedoch Strategien zur Anpassung an den Eisenmangel entwickelt. Sie “stehlen” zum Beispiel Eisen vom Wirt oder von anderen Bakterien durch spezifische Chelatoren mit einer hohen Affinität für Eisen. Die komplexen Wechselwirkungen zwischen Wirt und Pathogen zur Homöostase von Metallionen bieten zahlreiche Angriffspunkte für die Entwicklung neuer antibakterieller Wirkstoffe. Dieser Aufsatz ist auf Prozesse mit Eisenbeteiligung fokussiert. Es werden die neuesten Entwicklungen und mögliche Perspektiven für die Entwicklung von Antibiotikaresistenzen diskutiert.

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3-Acylated tetramic and tetronic acids as natural metal binders: myth or reality?

Cited by 39 publications

References 103 publications

Pyrrolocin C and equisetin inhibit bacterial acetyl-CoA carboxylase

Pyrrolocin C and equisetin inhibit bacterial acetyl-CoA carboxylase

X-Ray Crystallographic Analysis, EPR Studies, and Computational Calculations of a Cu(II) Tetramic Acid Complex

Chemische und biologische Aspekte von “Nutritional Immunity” – Perspektiven für neue Antiinfektiva mit Fokus auf bakterielle Eisenaufnahmesysteme

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