Lupane-Type Pentacyclic Triterpenes in Langmuir Monolayers: A Synchrotron Radiation Scattering Study

摘要

Lupane-type pentacyclic triterpenes (lupeol, betulin, and betulinic acid) arennatural products isolated from various plant sources. The terpenes exhibit a vast spectrumnof biological activity and are applied in therapies for different diseases, among which thenanticancer, anti-HIV, antihypercholesteremic, and antiinflammatory are the mostnpromising. These chemicals possess amphiphilic structure and were proved to interactnstrongly with biomembranes, which can be the key stage in their mechanism of action. Innour studies, we applied Langmuir monolayers as versatile models of biomembranes. Itnturned out that the three investigated terpenes are capable of stable monolayer formation;nhowever, these monolayers differ profoundly regarding their physicochemical characteristics.nIn our research, we applied the Langmuir technique (surface pressure−meannmolecular area (π−A) isotherm registration) coupled with Brewster angle microscopyn(BAM), but the main focus was on the synchrotron radiation scattering method, grazingnincidence X-ray diffraction (GIXD), which provides information on the amphiphilicnmolecule ordering in the angström scale. It was proved that all the investigated terpenesnform crystalline phases in their monolayers. In the case of lupeol, only the closely packed upright phase was observed, whereas fornbetulin and betulinic acid, the phase situation was more complex. Betulinic acid molecules can be organized in an upright phase,nwhich is crystalline, and in a tilted phase, which is amorphous. The betulin film is a conglomerate of an upright crystallinenmonolayer phase, tilted amorphous monolayer phase, and a crystalline tilted bilayer. In our paper, we discuss the factors leadingnto the formation of the observed phases and the implications of our results to the therapeutic applications of the native lupanetypentriterpenes.