Enhanced Solubility and Anticancer Potential of Mansonone G By β-Cyclodextrin-Based Host-Guest Complexation: A Computational and Experimental Study

Mansonone G (MG), a plant-derived compound isolated from the heartwood of Mansonia gagei, possesses a potent antitumor effect on several kinds of malignancy. However, its poor solubility limits the use for practical applications. Beta-cyclodextrin (beta CD), a cyclic oligosaccharide composed of seven (1 -> 4)-linked alpha-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 beta CD and its derivatives (2,6-di-O-methyl-beta CD (DM beta CD) and hydroxypropyl-beta CD). The 90-ns molecular dynamics simulations and MM/GBSA-based binding free energy results suggested that DM beta CD was the most preferential host molecule for MG inclusion complexation. The inclusion complex formation between MG and beta CD(s) was confirmed by DSC and SEM techniques. Notably, the MG/beta CDs inclusion complexes exerted significantly higher cytotoxic effect (similar to 2-7 fold) on A549 lung cancer cells than the uncomplexed MG.