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Open AccessArticle

Investigation of the Inhibition Potential of New Oxindole Derivatives and Assessment of Their Usefulness for Targeted Therapy

Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpinskiego 5, 85-096 Bydgoszcz, Poland
Symmetry 2019, 11(8), 974; https://doi.org/10.3390/sym11080974
Received: 29 June 2019 / Revised: 22 July 2019 / Accepted: 27 July 2019 / Published: 1 August 2019
(This article belongs to the Special Issue Applied Designs in Chemical Structures with High Symmetry)
Oxindole derivatives are a large group of compounds that can play the role of Adenosine triphosphate (ATP) competitive inhibitors. The possibility of modification of such compounds by addition of active groups to both cyclic systems of oxindole allows the obtaining of derivatives showing significant affinity toward cyclin-dependent kinase (CDK) proteins. Overexpression of that enzyme is observed in the case of most cancers. The discovery of new efficient inhibitors, which could be used in the development of targeted therapies, is one of the current goals setting trends in recent research. In this research, an oxindole molecular core was used, which was modified by the addition of different substituents to both side chains. The realized procedure allowed the creation of a set of oxindole derivatives characterized by binding affinity values and molecular descriptors evaluated during docking procedures and QSAR calculations. The most promising structures characterized by best sets of parameters were used during the molecular dynamics stage. The analysis of structural and energetic properties of systems obtained during this stage of computation gives an indication of inhibitors creating the most stable complexes, characterized by the highest affinity. During this stage, two structures were selected, where affinity towards potential nanocarriers was evaluated. Realized calculations confirmed a significant role of stacking interactions in the stabilization of ligand complexes with fullerene molecules. Obtained data indicates that complexes of oxindole derivatives and considered nanocarriers exhibit significant potential in the creation of immobilized drugs, and can be used in the development of targeted therapies. View Full-Text
Keywords: CDK-2; oxidoles; docking; molecular dynamics; MMPBSA; inhibition; C60 fullerene derivatives CDK-2; oxidoles; docking; molecular dynamics; MMPBSA; inhibition; C60 fullerene derivatives
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MDPI and ACS Style

Czeleń, P. Investigation of the Inhibition Potential of New Oxindole Derivatives and Assessment of Their Usefulness for Targeted Therapy. Symmetry 2019, 11, 974.

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