Computational exploration of novel indanone-pyrazole fused schiff base scaffolds as potential EGFR inhibitors for anticancer therapy

One of the most effective strategies for treating cancer is the discovery of molecular medicines that block particular processes in the growth of cancer cells.Since many malignancies exhibit over-activation of the epidermal growth factor receptor (EGFR), targeting EGFR and its downstream signaling cascades is thought to be a sensible and beneficial strategy for cancer treatment. Here, five novel indanone-pyrazole hybridized Schiff base scaffolds were designed and subjected to computational evaluation to identify potential EGFR inhibitors. In silico docking studies were conducted to evaluate the binding affinities and interactions of the designed congeners with the 1M17 protein active site. Furthermore, Lipinski analysis, ADMET profiling, toxicity profiling, molecular simulation study werecarried out of these novel compounds. According to the docking study, all lead compounds demonstrated strong binding energy (ranging from − 7.6 to − 8.6 kcal/mol) than native and standard drug (Neratinib). These Schiff base congeners revealed favorable physicochemical properties, high gastrointestinal absorption, low toxicity, and compliance with the Lipinski rule of five, suggesting their potential as effective therapeutic agents.The results of this study are of great interest for the rational design of new EGFR-targeted anticancer drugs and point to the need for additional in vitro and in vivo studies.