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

Abstract

Lupane-type pentacyclic triterpenes (lupeol, betulin, and betulinic acid) are natural products isolated from various plant sources. The terpenes exhibit a vast spectrum of biological activity and are applied in therapies for different diseases, among which the anticancer, anti-HIV, antihypercholesteremic, and antiinflammatory are the most promising. These chemicals possess amphiphilic structure and were proved to interact strongly with biomembranes, which can be the key stage in their mechanism of action. In our studies, we applied Langmuir monolayers as versatile models of biomembranes. It turned out that the three investigated terpenes are capable of stable monolayer formation; however, these monolayers differ profoundly regarding their physicochemical characteristics. In our research, we applied the Langmuir technique (surface pressure-mean molecular area (π-A) isotherm registration) coupled with Brewster angle microscopy (BAM), but the main focus was on the synchrotron radiation scattering method, grazing incidence X-ray diffraction (GIXD), which provides information on the amphiphilic molecule ordering in the angström scale. It was proved that all the investigated terpenes form crystalline phases in their monolayers. In the case of lupeol, only the closely packed upright phase was observed, whereas for betulin and betulinic acid, the phase situation was more complex. Betulinic acid molecules can be organized in an upright phase, which is crystalline, and in a tilted phase, which is amorphous. The betulin film is a conglomerate of an upright crystalline monolayer phase, tilted amorphous monolayer phase, and a crystalline tilted bilayer. In our paper, we discuss the factors leading to the formation of the observed phases and the implications of our results to the therapeutic applications of the native lupane-type triterpenes.

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

“…For Urs at 15 mN/m A = 42.6Å which is the value noticeably lower than 51.0Å, the limiting area A lim , which can be read from the -A isotherm. It is in accordance with the GIXD data collected for similar bolaamphiphilic terpenes: betulinic acid [31] and oleanolic acid [29]. It seems that similarly to these substances also in the monolayers of Urs there is an equilibrium between the crystalline upright phase in which the -OH groups are directed toward water and the LE tilted phase in which the molecules contact with water via the -COOH group.…”

“…Urs is a bolaamphiphilic terpene with two polar groups, -OH and -COOH at the termini of the stiff skeleton of fused cycloalkane ring. It was corroborated by us [31] and other authors [29,30] that such terpenes can acquire two competing conformations at the air/water interface. In a pure Urs monolayer both conformations are present even at higher surface pressure values leading to the formation of two 2D-phases: crystalline formed by upright molecules having their -OH group in contact with water and tilted LE phase with the -COOH group immersed in water.…”

“…The GIXD results provided important information about the structure of oleanolic acid one-component monolayers [29] and about its mixtures with stearic acid [30]. Following the pioneer studies we characterized the monolayers of the PT from lupane family: lupeol, betulin and betulinic acid, both in one-component monolayers [31] and in mixtures with phospholipids [32]. The monolayers of amyrins and ursolic acid have not been characterized by GIXD, so the preliminary aim of the present studies was to fill this gap and investigate the 2D-crystallinity at different steps of the film compression.…”

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.…”

Effect of Erythrodiol, A Natural Pentacyclic Triterpene from Olive Oil, on the Lipid Membrane Properties

“…The structure of a triterpenic compound (Dufourc 2008;Prades et al 2011;Rodriguez et al 1997), the number of oxidized groups Pownall 2005, 2006), and the conjugation to a sugar structure (Lorent et al 2013;Hu et al 1996) are the factors that control the interaction and consequently the effects of triterpenic molecules on the membrane properties. Among the natural pentacyclic triterpenes, many reports have been published concerning the interaction with lipid membrane of lupeol (Rodriguez et al 1997;Broniatowski et al 2012a, b), betulinic acid (Broniatowski et al 2012a, b), betulin (Broniatowski et al 2012a), oleanolic, maslinic, ursolic acids (Prades et al 2011;Han et al 1997), alpha-amyrin, and taraxerol (Rodriguez et al 1997).…”