Multiple docking of α-, β-, and γ- cyclodextrin with vinpocetine chiral complexes
Abstract
Cyclodextrin is a compound that is able to form inclusion complexes which modifies the properties of guest ligands such as vinpocetine in order to improve on its physical and chemical characteristics. The molecular docking method of various cyclodextrins with vinpocetine chiral complexes can be used to study on its different binding conformations and orientations which acts as a screening process that is hoped to be able to aid laboratory analysis to synthesize new and more efficient drugs. This study utilizes Autodock 4.2, which is an automatic docking program to study on the complexation reaction of α-, β-, and γ-cyclodextrin with vinpocetine stereoisomers. The docking structures are obtained from PubChem Compound Database and RCSB Protein Data Bank respectively. The aim of this study is to investigate on the most stable complexation formation and study on the different interactions of the complex stereoisomers formed from the simulation of single docking (1:1), and multiple docking (2:1) and (3:1), where one, two, and three different cyclodextrins are docked into a single vinpocetine respectively to study on the orientations, number of conformations, binding energies, and the number of intermolecular hydrogen bonding formations of the cyclodextrins with different stereoisomers of vinpocetine and determining the best possible combination with the lowest binding energies. The lowest binding energy, along with the highest number of conformations indicates that the structure is the most stable chiral complex that is likely to form. For single docking, the trend of binding energy from the least to most stable based on different CD-VP chiral complexes is 3S16S > 3S16R > 3R16S > 3R16R for α-CD, 3S16R > 3S16S > 3R16R > 3R16S for β-CD, 3S16R > 3S16S > 3R16R > 3R16S for γ-CD. For multiple docking in the ratio of 2:1 CD:VP, most complexes form a sandwich conformation with the trend being 3R16R α-CD-γ-CD > 3S16S β-CD-γ-CD > 3S16R β-CD-γ-CD > 3R16S α-CD-γ-CD > 3R16R β-CD-γ-CD > 3S16S α-CD-β-CD > 3R16S β-CD-γ-CD > 3S16R α-CD-γ-CD > 3R16R α-CD-β-CD > 3S16R α-CD-β-CD > 3R16S α-CD-β-CD > 3S16S α-CD-γ-CD. However, multiple docking in the 3:1 ratio of CD:VP show positive energy and are predicted to be unstable.
Keywords
Full Text:
PDFReferences
Szejtli, J. Cyclodextrins. In: Szejtli, J. ed. Cyclodextrin Technology. Dordrecht: Kluwer Academic Publishers. 45–82; 1988..
Sebestyén, Z., Buvári-Barcza, Á., and Rohonczy, J. (2012). pH-dependent complex formation of amino acids with b-cyclodextrin and quaternary ammonium b-cyclodextrin. J Incl Phenom Macro. 73:199-210.
Alkaloids, I. Ullmann’s Encyclopedia of Industrial Chemistry. 5th ed. Wiley-VCH A1.1997.
Szabó, L., Sápi, J., Kalaus, G., Argay, G., Kálmán, A., Baitz-Gács, E., Tamás, J. and Szántay, C. (1983). Newroute tothe stereoselective synthesis of β-vincamine, β-vincamone, and β-apovincaminic acid esters. Tetrahedron Letters.316: 629–638.
Ribeiro, L.S., Falcão, A.C., Patrício, J.A., Ferreira, D.C. and Veiga, F.J. (2007). Cyclodextrin multicomponent complexation and controlled release delivery strategies to optimize the oral bioavailability of vinpocetine. Journal of Pharmaceutical Sciences. 96(8): 2018-2028.
O’Driscoll, C.M., Griffin, B.T. (2008). Biopharmaceutical challenges associated with drugs with low aqueous solubility - The potential impact of lipid-based formulations. Advanced Drug Delivery Reviews. 60: 617–624.
Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson,A. J. (1998). Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 19: 1639.
Issaraseriruk, N., Shitangkoon, A. and Aree, T. (2010). Molecular Docking Study for the Prediction Of Enantiodifferentiation Of Chiral Styrene Oxides by octakis(2,3-di-O- acetyl-6-O-tesrt-butyldimenthylsilyl)-γ-cyclodextrin. Journal of Molecular Graphics and Modelling. 28: 506-512.
Zhang, H., Tan, T., Hetenyi, C. and David, S. (2013). Qualification of Solvent Contribution to the Stability of Noncovalent Complexes. Journal of Chemical Theory and Computation. 9: 4542−4551.
Refbacks
- There are currently no refbacks.
Copyright (c) 2017 eProceedings Chemistry
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright © 2016 Department of Chemistry, Universiti Teknologi Malaysia.
Disclaimer : This website has been updated to the best of our knowledge to be accurate. However, Universiti Teknologi Malaysia shall not be liable for any loss or damage caused by the usage of any information obtained from this web site.
Best viewed: Mozilla Firefox 4.0 & Google Chrome at 1024 × 768 resolution.