QSAR Study and Molecular Docking of 2 Phenylaminoimidazo[4,5-H] Isoquinolin-9-Ones as Potent Inhibitors of P56ick Tyrosine Kinase (LCK) in Breast Cancer Therapy

QSAR Study and Molecular Docking of 2 Phenylaminoimidazo[4,5-H] Isoquinolin-9-Ones as Potent Inhibitors of P56ick Tyrosine Kinase (LCK) in Breast Cancer Therapy

Author by Dr. John Afees Olanrewaju

Journal/Publisher: Journal Of Biomedical And Pharmaceutical Sciences

Volume/Edition: 1

Language: English

Pages: 108 - 117

Abstract

The advances of Quantitative Structure-Activity Relationship (QSAR) studies has made the design and development of novel drugs simplified and more cost effective. QSAR in combination with molecular docking is useful in rational drug design. QSAR and Molecular docking methods were performed on 2 phenylaminoimidazo[4,5-h]isoquinolin-9-ones as inhibitors of lck. Docking studies were employed with the aid of PyRx to position the inhibitors into the lck active site to determine the optimum binding conformation and to elucidate the interactions with amino acid residues within the active site of the receptor. Based on AutoDuck vina scoring function, Compound 18 show a better binding affinity compared to the co-crystallized ligand (PBD ID: PM3). Twenty-one (21) compounds (Training dataset=14 compounds, Test dataset=7 compounds) were selected for this study. The statistical regression expressions were obtained using Multiple Linear Regression (MLR) and Partial Least Squares (PLS) with the MLR method showing more promising result than the PLS method. A QSAR model is generated by the training dataset with correlation coefficient R2 of 0.79207, cross validation coefficient Q2 (LOO) of 0.66644, r2 (correlation coefficient) for the external dataset is 0.89699 while r2 of predicted dataset is 0.68432 by the Multiple Linear Regression Method.

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