Skip to main content
padlock icon - secure page this page is secure

Docking-based 3D-QSAR study of pyridyl aminothiazole derivatives as checkpoint kinase 1 inhibitors

Buy Article:

$61.00 + tax (Refund Policy)

Checkpoint kinase 1 (Chk1) is a promising target for the design of novel anticancer agents. In the present work, molecular docking simulations and three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were performed on pyridyl aminothiazole derivatives as Chk1 inhibitors. AutoDock was used to determine the probable binding conformations of all the compounds inside the active site of Chk1. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were developed based on the docking conformations and alignments. The CoMFA model produced statistically significant results with a cross-validated correlation coefficient (q 2) of 0.608 and a coefficient of determination (r 2) of 0.972. The reliable CoMSIA model with q 2 of 0.662 and r 2 of 0.970 was obtained from the combination of steric, electrostatic and hydrogen bond acceptor fields. The predictive power of the models were assessed using an external test set of 14 compounds and showed reasonable external predictabilities (r 2 pred) of 0.668 and 0.641 for CoMFA and CoMSIA models, respectively. The models were further evaluated by leave-ten-out cross-validation, bootstrapping and progressive scrambling analyses. The study provides valuable information about the key structural elements that are required in the rational design of potential drug candidates of this class of Chk1 inhibitors.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
No Metrics

Keywords: 3D-QSAR; Chk1; CoMFA; CoMSIA; docking; pyridyl aminothiazoles

Document Type: Research Article

Affiliations: Department of Bio-New Drug Development, College of Medicine, Chosun University, Gwangju, 501-759, Republic of Korea

Publication date: August 3, 2014

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more