Structural and Computational Biology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Biomolecules. 2019 Sep 27;9(10):545. doi: 10.3390/biom9100545.
Mansonone G (MG), a plant-derived compound isolated from the heartwood of , possesses a potent antitumor effect on several kinds of malignancy. However, its poor solubility limits the use for practical applications. Beta-cyclodextrin (βCD), a cyclic oligosaccharide composed of seven (1→4)-linked α-D-glucopyranose units, is capable of encapsulating a variety of poorly soluble compounds into its hydrophobic interior. In this work, we aimed to enhance the water solubility and the anticancer activity of MG by complexation with βCD and its derivatives (2,6-di--methyl-βCD (DMβCD) and hydroxypropyl-βCD). The 90-ns molecular dynamics simulations and MM/GBSA-based binding free energy results suggested that DMβCD was the most preferential host molecule for MG inclusion complexation. The inclusion complex formation between MG and βCD(s) was confirmed by DSC and SEM techniques. Notably, the MG/βCDs inclusion complexes exerted significantly higher cytotoxic effect (2-7 fold) on A549 lung cancer cells than the uncomplexed MG.
曼森酮 G（MG）是一种从 中提取的植物源性化合物，对多种恶性肿瘤具有强大的抗肿瘤作用。然而，其较差的溶解度限制了其在实际应用中的使用。β-环糊精（βCD）是由七个（1→4）连接的α-D-吡喃葡萄糖单元组成的环状低聚糖，能够将各种难溶化合物包合到其疏水性内部。在这项工作中，我们旨在通过与 βCD 及其衍生物（2,6-二甲基-βCD（DMβCD）和羟丙基-βCD）的络合来提高 MG 的水溶性和抗癌活性。90-ns 分子动力学模拟和基于 MM/GBSA 的结合自由能结果表明，DMβCD 是 MG 包合络合的最优先主分子。DSC 和 SEM 技术证实了 MG 与 βCD（s）之间的包合物形成。值得注意的是，MG/βCDs 包合物对 A549 肺癌细胞的细胞毒性作用（2-7 倍）明显高于未络合的 MG。
