Grazing incidence diffraction studies of the interactions between ursane-type antimicrobial triterpenes and bacterial anionic phospholipids

Broniatowski, Marcin; Flasiński, Michał; Wydro, Paweł; Fontaine, Philippe

doi:10.1016/j.colsurfb.2015.03.009

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…These results were discussed in reference to the biological activity of the studied compounds, pointing out that the molecular mechanism of biological activity of these terpenes may be membrane-related and that the charge of the anionic phospholipids may be a key factor for such interaction. Also, grazing incidence diffraction studies for the interactions between ursane-type antimicrobial triterpenes and bacterial anionic phospholipids 52 emphasized the significance of the interactions between the cyclopropane ring present in the hydrophobic part of the bacterial phospholipids and the terminal ring of the terpene structure. It was proposed that the significant differences between the systems with the triterpenes are connected with the formation of hydrogen bonds between the hydrophobic moieties.…”

Section: Resultsmentioning

confidence: 99%

Mechanism of Action of Thymol on Cell Membranes Investigated through Lipid Langmuir Monolayers at the Air–Water Interface and Molecular Simulation

et al. 2016

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A major challenge in the design of biocidal drugs is to identify compounds with potential action on microorganisms and to understand at the molecular level their mechanism of action. In this study, thymol, a monoterpenoid found in the oil of leaves of Lippia sidoides with possible action in biological surfaces, was incorporated in lipid monolayers at the air-water interface that represented cell membrane models. The interaction of thymol with dipalmitoylphosphatidylcholine (DPPC) at the air-water interface was investigated by means of surface pressure-area isotherms, Brewster angle microscopy (BAM), polarization-modulation reflection-absorption spectroscopy (PM-IRRAS), and molecular dynamics simulation. Thymol expands DPPC monolayers, decreases their surface elasticity, and changes the morphology of the lipid monolayer, which evidence the incorporation of this compound in the lipid Langmuir film. Such incorporation could be corroborated by PM-IRRAS since some specific bands for DPPC were changed upon thymol incorporation. Furthermore, potential of mean force obtained by molecular dynamics simulations indicates that the most stable position of the drug along the lipid film is near the hydrophobic regions of DPPC. These results may be useful to understand the interaction between thymol and cell membranes during biochemical phenomena, which may be associated with its pharmaceutical properties at the molecular level.

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Section: Resultsmentioning

confidence: 99%

Mechanism of Action of Thymol on Cell Membranes Investigated through Lipid Langmuir Monolayers at the Air–Water Interface and Molecular Simulation

et al. 2016

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“…However, as a result of the abuse of antibiotics, the constant increase of drug-resistant bacteria has become a great threat to animals and humans as well as a severe challenge to therapy. , It is meaningful to develop alternative new antibacterial agents without resistance. Recent studies focus on natural products because of their complex structure and multiple targeting mechanisms, − which can be exploited as antibiotic substitutes with a lower propensity of bacterial resistance.…”

Section: Introductionmentioning

confidence: 99%

Structure and Activity of the Camellia oleifera Sapogenin Derivatives on Growth and Biofilm Inhibition of Staphylococcus aureus and Escherichia coli

Zhu

Zhang

Tang

et al. 2019

J. Agric. Food Chem.

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Sapogenin is the main block of Camellia oleifera saponin, which was purified and structurally modified by the C28 acylation reaction to synthesize 19 new derivatives. The growth and biofilm inhibition of Staphylococcus aureus and Escherichia coli was measured to evaluate their antibacterial effects. A three-dimensional quantitative structure–activity relationship (3D-QSAR) assay indicated that the antibacterial activities were significantly enhanced after sapogenin was modified with an aromatic ring or heterocyclic ring and electron-withdrawing substituents at the meta or para position. Among them, the derivative of sapogenin with a 2-mercapto-4-methyl-5-thiazolyl acetyl group obviously destroyed bacterial biofilm and made bacteria lysis. 3D-QSAR provides practical information for the structural design of sapogenin derivatives with strong antibacterial activity, and the C. oleifera sapogenin derivative 28-O-(2-mercapto-4-methyl-5-thiazolyl)-3β,16α,21β,22α-O-tetrahydroxy-oleantel-2-ene-23-aldehyde (S-16) is an effective candidate as an antibacterial agent for the prevention of bacterial resistance against antibiotics.

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“…Ursanes and oleananes differ only in the location of one methyl group [ 58 ] and thus in number and location of chiral centers [ 60 ]. This could result in differences in the interaction with lipids and the possibility of H-bond formation with the cyclopropane ring of the hydrocarbon chain of phospholipids [ 61 ]. The degree of permeation of each molecule into the bilayer should be a compromise between the number of hydrophobic contacts and the cost of losing some H-bonds in water.…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, UA and OA are able to perturb critical biophysical membrane properties like fluidity and permeability. The disintegration of cardiolipin-enriched domains induced by UA [ 61 ] could be linked with PBP2a delocalization from the S. aureus septum induced by pentacyclic triterpenes [ 7 ]. The activity of the scaffold protein flotillin with reduction of the MRSA proliferative capacity in the presence of β-lactam antibiotics has also been reported in link with perturbation of functional membrane microdomains architecture and efficient PBP2a oligomerization [ 71 , 72 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes

et al. 2021

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Staphylococcus aureus is an opportunistic pathogen and the major causative agent of life-threatening hospital- and community-acquired infections. A combination of antibiotics could be an opportunity to address the widespread emergence of antibiotic-resistant strains, including Methicillin-Resistant S. aureus (MRSA). We here investigated the potential synergy between ampicillin and plant-derived antibiotics (pentacyclic triterpenes, ursolic acid (UA) and oleanolic acid (OA)) towards MRSA (ATCC33591 and COL) and the mechanisms involved. We calculated the Fractional Inhibitory Concentration Index (FICI) and demonstrated synergy. We monitored fluorescence of Bodipy-TR-Cadaverin, propidium iodide and membrane potential-sensitive probe for determining the ability of UA and OA to bind to lipoteichoic acids (LTA), and to induce membrane permeabilization and depolarization, respectively. Both pentacyclic triterpenes were able to bind to LTA and to induce membrane permeabilization and depolarization in a dose-dependent fashion. These effects were not accompanied by significant changes in cellular concentration of pentacyclic triterpenes and/or ampicillin, suggesting an effect mediated through lipid membranes. We therefore focused on membranous effects induced by UA and OA, and we investigated on models of membranes, the role of specific lipids including phosphatidylglycerol and cardiolipin. The effect induced on membrane fluidity, permeability and ability to fuse were studied by determining changes in fluorescence anisotropy of DPH/generalized polarization of Laurdan, calcein release from liposomes, fluorescence dequenching of octadecyl-rhodamine B and liposome-size, respectively. Both UA and OA showed a dose-dependent effect with membrane rigidification, increase of membrane permeabilization and fusion. Except for the effect on membrane fluidity, the effect of UA was consistently higher compared with that obtained with OA, suggesting the role of methyl group position. All together the data demonstrated the potential role of compounds acting on lipid membranes for enhancing the activity of other antibiotics, like ampicillin and inducing synergy. Such combinations offer an opportunity to explore a larger antibiotic chemical space.

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Grazing incidence diffraction studies of the interactions between ursane-type antimicrobial triterpenes and bacterial anionic phospholipids

Cited by 8 publications

References 34 publications

Mechanism of Action of Thymol on Cell Membranes Investigated through Lipid Langmuir Monolayers at the Air–Water Interface and Molecular Simulation

Mechanism of Action of Thymol on Cell Membranes Investigated through Lipid Langmuir Monolayers at the Air–Water Interface and Molecular Simulation

Structure and Activity of the Camellia oleifera Sapogenin Derivatives on Growth and Biofilm Inhibition of Staphylococcus aureus and Escherichia coli

Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes

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