biostudies-literatureUnknown30(5)Kandeel MMSTDF-RSG, EgyptA series of indolinone-based derivatives were designed and synthesized using the hybrid pharmacophoric design approach as cytotoxic kinase inhibitors. The cytotoxic effects of the designed molecules were tested against MCF-7 and HepG-2 cell lines. Compounds 9 and 20 were the most cytotoxic, with IC50 values against HepG-2 and MCF-7 cells ranging from 2.53 to 7.54 µM. Additionally, compounds 9 and 20 were also found to be slightly more cytotoxic than indirubin with 2.2-2.7-fold higher cytotoxicity with HepG-2 cells. CDK-2 and CDK-4 kinase enzyme inhibition assay showed that compound 9 had a higher inhibitory effect (4.8-fold) than indirubin against CDK-2 and comparable inhibition against CDK-4. Moreover, compound 20 displayed nanomolar inMolecules (Basel, Switzerland)1105https://www.ebi.ac.uk/biostudies/studies/S-EPMC11901902biostudies-literatureDesign, Synthesis, and Cytotoxicity Evaluation of Novel Indolin-2-One Based Molecules on Hepatocellular Carcinoma HepG2 Cells as Protein Kinase Inhibitors.PMC11901902AbdElhameid MKAl-Shorbagy MYKandeel MMAdel MNegmeldin ATfalseDesign, Synthesis, and Cytotoxicity Evaluation of Novel Indolin-2-One Based Molecules on Hepatocellular Carcinoma HepG2 Cells as Protein Kinase Inhibitors.A series of indolinone-based derivatives were designed and synthesized using the hybrid pharmacophoric design approach as cytotoxic kinase inhibitors. The cytotoxic effects of the designed molecules were tested against MCF-7 and HepG-2 cell lines. Compounds 9 and 20 were the most cytotoxic, with IC50 values against HepG-2 and MCF-7 cells ranging from 2.53 to 7.54 µM. Additionally, compounds 9 and 20 were also found to be slightly more cytotoxic than indirubin with 2.2-2.7-fold higher cytotoxicity with HepG-2 cells. CDK-2 and CDK-4 kinase enzyme inhibition assay showed that compound 9 had a higher inhibitory effect (4.8-fold) than indirubin against CDK-2 and comparable inhibition against CDK-4. Moreover, compound 20 displayed nanomolar in2025-01-01T00:00:00Z2025 Feb2026-04-08T19:48:44.913Z2025-04-04T09:08:14.277ZS-EPMC119019024007632910.3390/molecules30051105