Design, In Silico Molecular Docking, and ADMET Prediction of Amide Derivatives of Chalcone Nucleus as EGFR Inhibitors for the Treatment of Cancer.

Abstract

Cancer is a devastating disease. Many studies have shown that the primary causes of the aggressive and resistant types of cancer are the overexpression of receptors and growth factors, activation of oncogenes, and the inactivation of tumour suppressor genes. One such receptor is the epidermal growth factor receptor (EGFR), which is used as a drug target for the treatment of cancer. This study aimed to develop the new chemical entities of amide derivatives of chalcone as EGFR inhibitors using structure-activity relationship (SAR) studies, molecular docking, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) studies. New chemical entities (NCE) were designed based on literature findings. The Schrodinger 13.4 software was used for the molecular docking study. While Quickprop and Pro Tox-II online tools were used for ADME and toxicity prediction, respectively. In this work, all compounds were subjected to an in-silico ADMET analysis. After pharmacokinetic and toxicity profile predictions, the molecules were further analysed by molecular docking. As a result of molecular docking, molecules AC9 and AC19 showed comparable docking scores compared to standard Afatinib. Molecules AC9 and AC19 showed good docking scores and a promising ADMET profile. In the future, these derivatives can be further evaluated for wet lab studies and determination of their biological activity.