Synthesis, single-crystal, in vitro antitumor evaluation and molecular docking of 3-substitued 5,5-diphenylimidazolidine-2,4-dione derivatives

Series of 3-alkyl, 3-aryl-5,5-diphenylimidazolidine-2,4-diones (2-8) and 3-phenacyl-5,5-diphenylimidazolidine-2,4-diones (9-20) were designed, synthesized, and tested for their antitumor activity. The 13 compounds (3-8, 10-15 and 20) were selected by National Cancer Institute (USA) on the basis of degree of the structure variation and computer modeling techniques for evaluation of their antineoplastic activity. A single dose (10 mu M) of the tested compounds was used in the National Cancer Institute (NCI) 60 cell lines panel assay selected from different nine organs. The tested compounds possessed selective activity against the renal cancer (A498 and UO-31) cell lines. Interestingly, compound 13 showed moderate selective activities towards A498 and UO-31 cell lines, in addition to strong activity against melanoma (MDA-MB-435) cell line and breast cancer cell lines (MCF7) in 114 and 70 %, respectively. Molecular docking study was performed for the most active compound 13 to identify the structural features required for the antitumor activity. The results achieved can be used as a useful template for future development and further derivatization or modification to obtain more potent and selective antitumor agents. The development of novel molecules containing imidazolidine-2,4-dione pharmacophore have shown promising antitumor activities. Compound 13 exploited broad spectrum and potent antitumor activity with the percentages of inhibition range of 28-114 %.