Studies for development of novel quinazolinones: New biomarker for EGFR

•Novel quinazolinone has been identified by CADD analysis.•These novel molecules have shown good EGFR inhibitor properties in receptor–ligand interaction.•Appropriate biological activity was demonstrated by biological assays.•Structural and spectroscopic characterization.•Interaction with CDNA via intercalative mode of interaction.

The binding capabilities of a series of novel quinazolinone molecules were established and stated in a comprehensive computational methodology as well as by in vitro analysis. The main focus of this work was to achieve more insight of the interactions with crystal structure of PDB ID: 1M17 and predict their binding mode to EGFR. Three molecules were screened for further examination, which were synthesized and characterized using spectroscopic techniques. The persuasive affinity of these molecules towards EGFR inhibition (IC50 for QT = 45 nM) was established and validated from specific kinase assay including the cell viability spectrophotometric assay (QT = 12 nM). Drug likeliness property were also considered by analysing, the ADME of these molecules by using scintigraphic techniques. The result showed antitumour activity of QT (4.17 tumour/muscle at 4 h). Further photo physical properties were also analysed to see in vitro HSA binding to QT.

Graphical abstractDevelopment of novel quinazolinone molecules as potential EGFR inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide