In Silico Exploration of Aryl Halides Analogues as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and ADMET Screening

Abstract

Purpose: In this review, a set of aryl halides analogs were identified as potent checkpoint kinase 1 (Chk1) inhibitors through a series of computer-aided drug design processes, to develop models with good predictive ability, highlight the important interactions between the ligand and the Chk1 receptor protein and determine properties of the new proposed drugs as Chk1 inhibitors agents.

Methods: Three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling, molecular docking and absorption, distribution, metabolism, excretion and toxicity (ADMET) approaches are used to determine structure activity relationship and confirm the stable conformation on the receptor pocket.

Results: The statistical analysis results of comparative -molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models that employed for a training set of 24 compounds gives reliable values of Q ² (0.70 and 0.94, respectively) and R ² (0.68 and 0.96, respectively).

Conclusion: Computer–aided drug design tools used to develop models that possess good predictive ability, and to determine the stability of the observed and predicted molecules in the receptor pocket, also in silico of pharmacokinetic (ADMET) results shows good properties and bioavailability for these new proposed Chk1 inhibitors agents.