Molecular docking and 3D-QSAR studies on checkpoint kinase 1 inhibitors

Abstract

Checkpoint kinase 1(Chk1) is a promising target for cancer treatment. Here three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were performed on 174 1,4-dihydroindeno[1,2-c]pyrazole inhibitors of Chk1 using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Two satisfactory ligand-based QSAR models were built (CoMFA model: q2 = 0.541, r2 = 0.880, CoMSIA model: q2 = 0.590, r2 = 0.902). The docking-based studies presented a detailed understanding of interaction between the inhibitors and Chk1. The obtained QSAR models are highly predictable (CoMFA model: q2 = 0.567, r2 = 0.891, CoMSIA model: q2 = 0.596, r2 = 0.917). The models were further validated by an external testing set obtaining \( r_{\text{pred}}^{2} \) values 0.896 and 0.923 for CoMFA and CoMSIA, respectively. So our models might be helpful for further modification of 1,4-dihydroindeno[1,2-c]pyrazole derivatives.