Synthesis, anticancer, apoptosis-inducing activities and EGFR and VEGFR2 assay mechanistic studies of 5,5-diphenylimidazolidine-2,4-dione derivatives: Molecular docking studies

Abstract

A new series of 5,5-diphenylhydantoin derivatives containing benzylidene or isatin (<b>4</b>-<b>19</b>) was synthesized. Their anticancer activity against HeLa, a cervical cancer cell line, A549, a lung cancer cell line, and MDA-MB-231, a breast cancer cell line, was evaluated. Compounds <b>13</b>, <b>16</b>, <b>17</b> and <b>18</b> exhibited potent anticancer activity with average IC₅₀ values against the tested cell lines of 109, 59, 81 and 113 μM, respectively. Compound <b>16</b> showed potent EGFR and VEGFR2 inhibitory activity with IC₅₀ values of 6.17 and 0.09 μM, respectively. In addition, compound <b>16</b> induced caspase-dependent apoptosis and reactive oxygen species (ROS) production at 5 and 10 μM. Moreover, a molecular docking simulation was performed for compound <b>16</b> and sunitinib to predict the protein-ligand interactions with the active site of VEGFR2.