Synthesis and in vitroanticancer activity of some 2-oxindoline derivatives as potential CDK2 inhibitors

AbstractNovel series of 2-oxindoline hydrazones 6a–h, 3-hydroxy-2-oxoindolines 9a–dand 2-oxoindolin-3-ylidenes 10a–dwere prepared and assessed for their anticancer activity towards breast cancer cell line (MCF7). Compounds 6c, 6d, 6g, 9d, 10aand 10b(IC50= 14.0 ± 0.7, 15.6 ± 0.7, 13.8 ± 0.7, 4.9 ± 0.2, 6.0 ± 0.3 and 10.8 ± 0.5 µM, respectively) showed the highest growth inhibition activity against MCF7 when compared to staurosporine (IC50= 14.5 ± 0.7 µM). Cell cycle analysis exposed arrest at G1 phase for compounds 6c, 10and 10b, at S phase for compounds 6dand 9d, and at G1/S phase for compound 6g. Apoptotic effect of compounds 6c, 6d, 6g, 9d, 10aand 10bwas confirmed viatheir early and late apoptotic effects. A safety profile was revealed for compounds 6c, 6d, 6g, 9d, 10aand 10bon MCF10A treated normal cell. Also, compounds 6cand 10bdisplayed a promising CDK2 inhibition activity (IC50= 0.22 ± 0.01, 0.25 ± 0.01 µM, respectively). Also, docking study revealed comparable interactions with the native ligand (5-bromoindirubin). ADMET computational studies forecast the promising pharmacokinetic profile of the targeted compounds.Communicated by Ramaswamy H. Sarma