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

Abstract

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 <i>in vitro</i> biological assessment of two sets of 3-methylbenzofurans (<b>4a-d</b>, <b>6a-c</b>, <b>8a-c</b> and <b>11</b>) and 3-(morpholinomethyl)benzofurans (<b>15a-c</b>, <b>16a-b</b>, <b>17a-b</b> and <b>18</b>) 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 (<b>4b</b>, <b>15a</b> and <b>16a</b>) were further investigated for their effects on the cell cycle progression and apoptosis in A549 (for <b>4b</b>) and NCI-H23 (for <b>15a</b> and <b>16a</b>) cell lines. Furthermore, benzofurans <b>4b</b>, <b>15a</b> and <b>16a</b> displayed good VEGFR-2 inhibitory activity with IC₅₀ equal 77.97, 132.5 and 45.4 nM, respectively.