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

• Main Authors: Hamad M. Alkahtani, Mohammed M. Alanazi, Fadilah Sfouq Aleanizy, Fulwah Yahya Alqahtani, Ali Alhoshani, Fawaz E. Alanazi, Abdulrahman A. Almehizia, Ashraf N. Abdalla, Mashael G. Alanazi, Adel S. El-Azab, Alaa A.-M. Abdel-Aziz
• Format: Article
• Language: English
• Published: Elsevier 2019-07-01
• Series: Saudi Pharmaceutical Journal
• Online Access: http://www.sciencedirect.com/science/article/pii/S1319016419300532
• ISSN: 1319-0164

A new series of 5,5-diphenylhydantoin derivatives containing benzylidene or isatin (4–19) 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 13, 16, 17 and 18 exhibited potent anticancer activity with average IC50 values against the tested cell lines of 109, 59, 81 and 113 μM, respectively. Compound 16 showed potent EGFR and VEGFR2 inhibitory activity with IC50 values of 6.17 and 0.09 μM, respectively. In addition, compound 16 induced caspase-dependent apoptosis and reactive oxygen species (ROS) production at 5 and 10 μM. Moreover, a molecular docking simulation was performed for compound 16 and sunitinib to predict the protein-ligand interactions with the active site of VEGFR2. Keywords: 5,5-Diphenylhydantoin, Isatin, Apoptosis, EGFR, VEGFR2, Molecular docking