Molecular insights into inclusion complexes of mansonone E and H enantiomers with various β-cyclodextrins

Panupong Mahalapbutr; Bodee Nutho; Peter Wolschann; Warinthorn Chavasiri; Nawee Kungwan; Thanyada Rungrotmongkol

doi:10.1016/j.jmgm.2017.11.006

Molecular insights into inclusion complexes of mansonone E and H enantiomers with various β-cyclodextrins

J Mol Graph Model. 2018 Jan:79:72-80. doi: 10.1016/j.jmgm.2017.11.006. Epub 2017 Nov 11.

Authors

Panupong Mahalapbutr¹, Bodee Nutho², Peter Wolschann³, Warinthorn Chavasiri⁴, Nawee Kungwan⁵, Thanyada Rungrotmongkol⁶

Affiliations

¹ Structural and Computational Biology Research Group, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
² Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
³ Structural and Computational Biology Research Group, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, 1090, Austria; Institute of Theoretical Chemistry, University of Vienna, Vienna, 1090, Austria.
⁴ Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
⁵ Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand; Research Center on Chemistry for Development of Health Promoting Products from Northern Resources, Chiang Mai University, Chiang Mai, 50200, Thailand.
⁶ Structural and Computational Biology Research Group, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand; Program in Bioinformatics and Computational Biology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand. Electronic address: thanyada.r@chula.ac.th.

PMID: 29154164
DOI: 10.1016/j.jmgm.2017.11.006

Abstract

The structural dynamics and stability of inclusion complexes of mansonone E (ME) and H (MH) including their stereoisomers with various βCDs (methylated- and hydroxypropylated-βCDs) were investigated by classical molecular dynamics (MD) simulations and binding free energy calculations. The simulation results revealed that mansonones are able to form inclusion complexes with βCDs. The guest molecules are not completely inserted into the host cavity, their preferably positions are nearby the secondary rim with the oxane ring dipping into the hydrophobic inner cavity. The encapsulation process leads to a higher rigidity of the βCDs enhancing the intramolecular hydrogen bond formation ability and decreasing the chance of glucopyranose rotation. According to the MM-PBSA binding free energy calculation, all considered inclusion complexes are stable and the binding energies are mainly caused by van der Waals interactions. Moreover, the free energy calculations showed significant differences in the complexation energies for the stereoisomers, which could enable the separation of the isomers by analytical techniques for further pharmaceutical applications.

Keywords: Cyclodextrins; Inclusion complex; MM/PBSA; Mansonone E; Mansonone H; Molecular dynamics simulation; Naphthoquinone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ligands
Molecular Conformation
Molecular Dynamics Simulation*
Molecular Structure*
Naphthoquinones / chemistry*
Sesquiterpenes / chemistry*
Stereoisomerism
Water / chemistry
beta-Cyclodextrins / chemistry*

Substances

Ligands
Naphthoquinones
Sesquiterpenes
beta-Cyclodextrins
mansonone E
mansonone H
Water