Computational study on the molecular inclusion of andrographolide by cyclodextrin
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Due to the poor water solubility of andrographolide (andro), an inclusion technique has been developed to modify its physical and chemical properties so as to improve its bioavailability. In contrast with the immense experimental studies on the inclusion complexes of andro:cyclodextrin, no computational study has so far been carried out on this system. In this work, preliminary docking experiments with AutoDock were performed. Density Functional Theory (DFT) and Austin Model 1 (AM1) calculations upon the docking instances were applied to investigate the two possible modes of molecular inclusions between andro and x-cyclodextrin (xCD, where x is α, β or γ). Atoms-in-Molecules (AIM) analysis based on the B3LYP/cc-pVDZ wavefunction was applied to verify the existence of the intermolecular hydrogen bonds. It was found that the most stable complex among the six possible inclusion complexes was the one formed between andro and βCD with andro’s decalin ring moiety wrapped by CD at a ratio of 1:1. The hydrogen bonds between andro and CD were responsible for the stability of the inclusion complexes. The calculated data were found to be consistent with the experimental results. Thus, the results of this study can aid new drug design processes.
KeywordsAndrographolide Cyclodextrin Inclusion complex Hydrogen bond
This work was fully supported by a Strategic Research Grant from the City University of Hong Kong (Project No. 7002109). Financial supports for the purchase of a computational device from the Innovation and Technology Fund (Project No. GHP/070/05) of Hong Kong Government is also acknowledged. The authors would also like to express their gratitude to Dr N.B. Wong for his advice and support on the calculation part of this work.
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