Faculty of Chemistry, Jagiellonian University, Kraków, Poland.
Langmuir. 2012 Mar 20;28(11):5201-10. doi: 10.1021/la300024f. Epub 2012 Mar 6.
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.
羽扇豆烷型五环三萜（羽扇豆醇、白桦醇和白桦酸）是从各种植物来源中分离得到的天然产物。这些萜类化合物表现出广泛的生物活性，被应用于治疗各种疾病，其中抗癌、抗 HIV、抗高胆固醇血症和抗炎作用最有前途。这些化学物质具有两亲性结构，已被证明与生物膜强烈相互作用，这可能是它们作用机制的关键阶段。在我们的研究中，我们应用 Langmuir 单层作为生物膜的多功能模型。结果表明，三种研究的萜类化合物能够稳定形成单层；然而，这些单层在物理化学特性方面存在显著差异。在我们的研究中，我们应用了 Langmuir 技术（表面压力-平均分子面积（π-A）等温线记录）与布鲁斯特角显微镜（BAM）相结合，但主要关注点是同步辐射散射方法，掠入射 X 射线衍射（GIXD），它提供了关于在埃尺度上两亲分子有序的信息。事实证明，所有研究的萜类化合物在其单层中都形成结晶相。在羽扇豆醇的情况下，仅观察到紧密堆积的直立相，而对于白桦醇和白桦酸，相态情况更为复杂。白桦酸分子可以组织成直立相，这是结晶的，以及倾斜相，这是无定形的。白桦醇膜是直立结晶单层相、倾斜无定形单层相和结晶倾斜双层相的聚集体。在我们的论文中，我们讨论了导致观察到的相形成的因素，以及我们的结果对天然羽扇豆烷型三萜类化合物治疗应用的影响。
