DOCKING – BASED VIRTUAL SCREENING OF LIPINSKI COMPLIANT 2 -ARYLQUINA-ZOLIN – 4 – ONE DERIVATIVES: A MOMENTUM TO THE DISCOVERY OF NOVEL EGFR INHIBITORSAbstract
The epidermal growth factor receptor (EGFR), which is a potential anticancer drug target, is over-expressed in non-small-cell lung cancer (NSCLC). The present study is an attempt to explore the human EGFR (protein data bank code: 1M17) inhibition potential of Lipinski compliant compounds possessing 2-arylquinazoli-4-one scaffold with chalcone structural motif; by docking analysis, using Auto Dock 4.0 and Discovery Studio Visualizer. Docking experiments were validated by docking the reported co-crystallized erlotinib confermer at the active site of a target protein. The root means square deviation (RMSD) calculated for the docked co-crystallized confermer by using UCSF chimera was 0.989Ao. Five compounds C21, C42, C47, C10, and C46, were found as the most potent in-silico EGFR inhibitors and their free energy of binding (BE) came in the range of -45.56 kJ/mol to -41.25 kJ/mol. Absorption and toxicity predictions of the compounds were done using ad met SAR, an online prediction tool. The BE of the reference compound afatinib was found to be -32.72 kJ/mol. The understanding of protein-legend interactions would give accurate guidance for the rapid development of low molecular weight EGFR inhibitors.