Next Article in Journal
Quinazolin-4(3H)-ones and 5,6-Dihydropyrimidin-4(3H)-ones from β-Aminoamides and Orthoesters
Next Article in Special Issue
The Internal Relation between Quantum Chemical Descriptors and Empirical Constants of Polychlorinated Compounds
Previous Article in Journal
A Genomic Survey of Angiotensin-Converting Enzymes Provides Novel Insights into Their Molecular Evolution in Vertebrates
Previous Article in Special Issue
Study of the Applicability Domain of the QSAR Classification Models by Means of the Rivality and Modelability Indexes
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(11), 2924;

Molecular Modeling and Design Studies of Purine Derivatives as Novel CDK2 Inhibitors

School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
Author to whom correspondence should be addressed.
Academic Editor: Kok Hwa Lim
Received: 23 September 2018 / Revised: 29 October 2018 / Accepted: 6 November 2018 / Published: 9 November 2018
(This article belongs to the Special Issue QSAR and QSPR: Recent Developments and Applications)
Full-Text   |   PDF [14847 KB, uploaded 9 November 2018]   |  


Cyclin-dependent kinase 2 (CDK2) is a potential target for treating cancer. Purine heterocycles have attracted particular attention as the scaffolds for the development of CDK2 inhibitors. To explore the interaction mechanism and the structure–activity relationship (SAR) and to design novel candidate compounds as potential CDK2 inhibitors, a systematic molecular modeling study was conducted on 35 purine derivatives as CDK2 inhibitors by combining three-dimensional quantitative SAR (3D-QSAR), virtual screening, molecular docking, and molecular dynamics (MD) simulations. The predictive CoMFA model (q2 = 0.743, r pred 2 = 0.991), the CoMSIA model (q2 = 0.808, r pred 2 = 0.990), and the Topomer CoMFA model (q2 = 0.779, r pred 2 = 0.962) were obtained. Contour maps revealed that the electrostatic, hydrophobic, hydrogen bond donor and steric fields played key roles in the QSAR models. Thirty-one novel candidate compounds with suitable predicted activity (predicted pIC50 > 8) were designed by using the results of virtual screening. Molecular docking indicated that residues Asp86, Glu81, Leu83, Lys89, Lys33, and Gln131 formed hydrogen bonds with the ligand, which affected activity of the ligand. Based on the QSAR model prediction and molecular docking, two candidate compounds, I13 and I60 (predicted pIC50 > 8, docking score > 10), with the most potential research value were further screened out. MD simulations of the corresponding complexes of these two candidate compounds further verified their stability. This study provided valuable information for the development of new potential CDK2 inhibitors. View Full-Text
Keywords: CDK2; 3D-QSAR; virtual screening; molecular docking; lead compound optimization; molecular dynamics CDK2; 3D-QSAR; virtual screening; molecular docking; lead compound optimization; molecular dynamics

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Zhang, G.; Ren, Y. Molecular Modeling and Design Studies of Purine Derivatives as Novel CDK2 Inhibitors. Molecules 2018, 23, 2924.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top