Langmuir monolayer studies of the interaction of monoamphiphilic pentacyclic triterpenes with anionic mitochondrial and bacterial membrane phospholipids — Searching for the most active terpene

Abstract

The interactions of three representative monoamphiphilic pentacyclic triterpenes (PTs) with cardiolipins (CL) and phosphatidylglycerols (PG) extracted from mitochondrial and bacterial membranes were comparatively characterized in binary Langmuir monolayers. The studied terpenes: lupeol, α- and β-amyrin are isomeric compounds known from their broad biological activity. Anticancer and antimicrobial activity of PTs is often correlated with their propensity of being incorporated into mitochondrial and bacterial membranes and their specific interactions with cardiolipins. In our studies on 18 model systems surface pressure (π)-mean molecular area (A) isotherms were registered at five different component proportions in each system. Thermodynamic analysis complemented by in situ Brewster angle microscopy visualization of the investigated mixed films enabled the thorough characterization of the studied systems. It turned out that the investigated terpenes interact more favorably with PG molecules as compared to CLs. For most of the system containing CLs the values of ΔG(exc) were positive which was interpreted as the ability of the terpenes to disintegrate the membranes rich in CLs. Our results confirmed also that in the light of thermodynamic criterion α-amyrin exhibited the highest potential to disintegrate the CL containing domains in mitochondrial and bacterial membranes. The probable origin of the observed specific interactions between α-amyrin and investigated phospholipids could be explained based on the phenomenon of chiral discrimination. The obtained results were also widely discussed in reference to the biological activity of the studied compounds.

Dexibuprofen Biodegradable Nanoparticles: One Step Closer towards a Better Ocular Interaction Study

“…Collapse pressure values are very similar and do not differ significantly from the π c obtained for pure cholesterol monolayer (around 46 mN•m −1 ) [43]. This suggests some immiscibility phenomena [43][44][45] according with the presence of two domains. C −1 s values allow us to postulate that PEG mainly mixes with phospholipid-rich domains.…”

Enhanced Antibacterial Activity of Ent-Labdane Derivatives of Salvic Acid (7α-Hydroxy-8(17)-ent-Labden-15-Oic Acid): Effect of Lipophilicity and the Hydrogen Bonding Role in Bacterial Membrane Interaction

“…Further membrane-diterpene interaction studies have been performed, specifically in labdanes, e.g., sclareol, labd-7,13-dien-15-ol, and labd-13-ene-8α,15-diol, [ 27 , 28 ], (8 R ,13 S )-labdane-8,15-diol and (8 R ,13 R )-labdane-8,15-diol [ 29 ], myriadenolide [ 30 ], as well as antibacterial diterpenes that interact with bacterial membrane models, e.g., (+)-totarol, [ 31 , 32 ] and abietic acid [ 33 , 34 ], demonstrating that lipophilicity plays an important role in addition to structural factors. Also, among natural pentacyclic triterpenes, many reports have been published concerning the interaction between the lipid membrane and lupane triterpenoids [ 35 , 36 , 37 , 38 , 39 , 40 ]. The common functionality in these compounds is the hydroxyl group at C3.…”

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

“…It was reported in our previous paper [20] that the two-dimensional free energies of mixing, G exc , in the systems AMalf/ECCL and AMalf/ECPG have positive sign and high values for all the investigated proportions of the components. Therefore, taking into consideration this thermodynamic criterion, phase separation is probable in these systems.…”

“…Regardless of the exact mechanism of the PT activity, the membrane is the first place of their contact with the cell. Therefore, in previous studies we focused our attention on the PT-cellular membrane interactions and performed experiments regarding the interactions of selected PT with cardiolipins and phosphatidylglycerols, which are anionic phospholipids typical of mitochondrial and bacterial membranes [20,21]. Our preliminary studies performed with the application of the Langmuir monolayer technique proved that AMalf and Urs interact preferentially with ECCL, a natural cardiolipin extracted from Escherichia coli, and ECPG, a natural E. coli phosphatidylglycerol.…”