2D-QSAR study and design of novel pyrazole derivatives as an anticancer lead compound against A-549, MCF-7, HeLa, HepG-2, PaCa-2, DLD-1

Abstract

In this study, a local quantitative structure–activity relationship (QSAR) models were developed for set of compounds tested for their inhibitory activity against six different cancer cell lines viz. A-549, MCF-7, HeLa, HepG-2, PaCa-2 and DLD-1. Two different statistical approaches Principal Component Analysis (PCA) and Partial Least Square (PLS) analyses were employed to developed QSAR models. Further, activity predictions were carried out for in-house synthesized 63 pyrazole derivatives. Prediction of pIC50 value of all 63 synthesized pyrazole derivatives were estimated based on the most significant QSAR model developed for each cancer cell line. Several statistical parameters such as correlation coefficient R2, RMSE, Cross validated R2, Cross validated RMSE, internal validation Q2 and the external validation R2 revealed that developed models showed a significant value for explaining an acceptable QSAR model. The results derived highlighted some important compounds for being the most promise lead candidate against the six-cancer cell line with a significant pIC50 value. Considering the contribution of most important descriptors, we have designed new molecules which found to have greater inhibitory potentiality than the reference compounds. Overall, the results suggest that the developed QSAR models might be useful as a theoretical reference for experimental studies and designing more potent anti-cancer therapeutic pyrazoles based compounds.