Synthesis, biological evaluation and molecular docking studies of 1,3-benzoxazine derivatives as potential anticancer agents

A series of 6 and/or 8-substituted derivatives of 1,3-benzoxazines, having flavone moiety at 3-position, have been synthesized. For synthesis of the compounds, 6 or/and 8-substituted saliscylaldehydes were reacted with aminoflavone followed by reduction, and CHCl3/HCHO promoted cyclization to give corresponding aminoflavone precursors which provided the desired 1,3-benzoxazine skeleton. Cytotoxic effects of the synthesized compounds were investigated in vitro against human breast cancer (MCF-7) cell lines. Among the compounds tested, methyl (3f and 6f), methoxy (3h, 3i, and 6h), and chloro (3d) derivatives were found to be most potent with IC50 values of 14.3, 14.9, 17.1, 8.03, 12.1, and 12.03 μM, respectively. Molecular docking studies of most active compounds of the series revealed that they bind to a narrow hydrophobic pocket of the N-terminal chain in the ATP binding site of EGFR.