Development of 3-methyl/3-(morpholinomethyl)benzofuran derivatives as novel antitumor agents towards non-small cell lung cancer cells.

As one of the most lethal malignancies, lung cancer is considered to account for approximately one-fifth of all malignant tumours-related deaths worldwide. This study reports the synthesis and in vitro biological assessment of two sets of 3-methylbenzofurans ( 4a-d , 6a-c , 8a-c and 11 ) and 3-(morpholinomethyl)benzofurans ( 15a-c , 16a-b , 17a-b and 18 ) as potential anticancer agents towards non-small cell lung carcinoma A549 and NCI-H23 cell lines, with VEGFR-2 inhibitory activity. The target benzofuran-based derivatives efficiently inhibited the growth of both A549 and NCI-H23 cell lines with IC50 spanning in ranges 1.48-47.02 and 0.49-68.9 µM, respectively. The three most active benzofurans ( 4b , 15a and 16a ) were further investigated for their effects on the cell cycle progression and apoptosis in A549 (for 4b ) and NCI-H23 (for 15a and 16a ) cell lines. Furthermore, benzofurans 4b , 15a and 16a displayed good VEGFR-2 inhibitory activity with IC50 equal 77.97, 132.5 and 45.4 nM, respectively.