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

ABSTRACT: 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 (?CD), a cyclic oligosaccharide composed of seven (1?4)-linked ?-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 ?CD and its derivatives (2,6-di-O-methyl-?CD (DM?CD) and hydroxypropyl-?CD). The 90-ns molecular dynamics simulations and MM/GBSA-based binding free energy results suggested that DM?CD was the most preferential host molecule for MG inclusion complexation. The inclusion complex formation between MG and ?CD(s) was confirmed by DSC and SEM techniques. Notably, the MG/?CDs inclusion complexes exerted significantly higher cytotoxic effect (2-7 fold) on A549 lung cancer cells than the uncomplexed MG.

SUBMITTER: Mahalapbutr P 

PROVIDER: S-EPMC6843486 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature