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Molecules 2016, 21(5), 591; doi:10.3390/molecules21050591

In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations

School of Chemistry and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
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Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 30 March 2016 / Revised: 11 April 2016 / Accepted: 28 April 2016 / Published: 5 May 2016
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Checkpoint kinase 1 (Chk1) is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q2 values (0.531, 0.726), fitted correlation r2 coefficients (higher than 0.90), and standard error of prediction (less than 0.250). These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity. View Full-Text
Keywords: Chk1 protein; docking; CoMFA; CoMSIA; molecular dynamics Chk1 protein; docking; CoMFA; CoMSIA; molecular dynamics
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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).

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Gao, X.; Han, L.; Ren, Y. In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations. Molecules 2016, 21, 591.

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