Interactions of pentacyclic triterpene acids with cardiolipins and related phosphatidylglycerols in model systems

Abstract

Pentacyclic triterpene acids (PTAs): betulinic (BAc), oleanolic (Ola) and ursolic (Urs) are potent pharmaceuticals applied in the therapy of cancer and bacterial infections. The mechanism of PTA action is multifactor, but the important step is their interaction with the lipids of mitochondrial and bacterial membranes. In our studies we applied the Langmuir monolayer technique to investigate the interactions between PTAs and cardiolipins (CLs) and phosphatidylglycerols (PGs). We applied two different mammalian mitochondrial CLs and one species extracted from the membrane of Escherichia coli. For comparison we performed the same experiments on the systems containing PTAs and 3 PGs strictly correlated structurally to the applied CLs. Our studies proved that PTAs can disturb the organization of CL-rich domains and affect the bacterial membrane fluidity by the interactions with phosphatidylglycerols, so anionic phospholipids are the targets of their membrane action. The thermodynamic interpretation of the results indicated that Urs has the highest membrane disorganizing potential among the 3 studied PTAs. The studies performed on model systems proved also that BAc can discriminate over structurally similar animal cardiolipin species, interacts specifically with BHCL - the main mammalian CL and can disturb its organization in the membrane. In contrast, Ola and Urs are much active as far as the interaction with bacterial CLs and PGs is concerned.

ViscumTT induces apoptosis and alters IAP expression in osteosarcoma in vitro and has synergistic action when combined with different chemotherapeutic drugs

“…However, this observation leads to the hypothesis that triterpenic acids improve the uptake of viscum, which could also be one explanation for the synergistic effect. Triterpenic acids are able to embed in cell membranes, which leads to their disturbance [50, 51], and interact with anionic phospholipids [52]. Further investigations of this are necessary.…”

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

“…The intensity is comparable for pure one-component Urs monolayer and the binary films at Urs/phospholipid 4/1 and 2/1 proportions. This fact should be discussed together with the significant condensation effect observed for binary films at these Urs/phospholipid proportions [21]. Compression moduli (SFig.…”

“…On the other hand, the linear fall of the intensity with decreasing X(Urs) corroborates phase separation in the binary monolayers. In our previous paper [21] we discussed the G exc -X(Urs) dependences in the system Urs/ECCL. The sign of G exc was positive, similarly to the system AMalf/ECCL.…”

“…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.…”

Crucial Role of the Double Bond Isomerism in the Steroid B-Ring on the Membrane Properties of Sterols. Grazing Incidence X-Ray Diffraction and Brewster Angle Microscopy Studies

“…30,31 Interestingly, this similarity of the discussed surface properties could be connected to the presence of two methyl groups attached to the C4 carbon atom, being a common structural motif found in cycloalkane skeletons of both lanosterol and pentacyclic triterpenes.…”