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.