Design, Synthesis, and Cytotoxicity Evaluation of Novel Indolin-2-One Based Molecules on Hepatocellular Carcinoma HepG2 Cells as Protein Kinase Inhibitors DOI Creative Commons

Manal M. Kandeel,

Mohammed K. Abdelhameid, Mohamed A. Said

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(5), P. 1105 - 1105

Published: Feb. 28, 2025

A series of indolinone-based derivatives were designed and synthesized using the hybrid pharmacophoric design approach as cytotoxic kinase inhibitors. The effects molecules tested against MCF-7 HepG-2 cell lines. Compounds 9 20 most cytotoxic, with IC50 values cells ranging from 2.53 to 7.54 µM. Additionally, compounds also found be slightly more than indirubin 2.2-2.7-fold higher cytotoxicity cells. CDK-2 CDK-4 enzyme inhibition assay showed that compound had a inhibitory effect (4.8-fold) comparable CDK-4. Moreover, displayed nanomolar action both EGFR VFGFR-2 enzyme, which around 8.8- 5.4-fold indirubin. induced cycle arrest at G1 phase on HepG2 levels key apoptotic proteins assessed revealed elevated Bax/Bcl-2 ratio, in turn initiated caspase3/7 cascade led activation intrinsic extrinsic pathways. p53 p21 significantly upregulated upon treatment 20. docking results exhibits stronger binding affinity indirubin, similar mode sorafenib VEGFR-2.

Language: Английский

Design, Synthesis, and Cytotoxicity Evaluation of Novel Indolin-2-One Based Molecules on Hepatocellular Carcinoma HepG2 Cells as Protein Kinase Inhibitors DOI Creative Commons

Manal M. Kandeel,

Mohammed K. Abdelhameid, Mohamed A. Said

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(5), P. 1105 - 1105

Published: Feb. 28, 2025

A series of indolinone-based derivatives were designed and synthesized using the hybrid pharmacophoric design approach as cytotoxic kinase inhibitors. The effects molecules tested against MCF-7 HepG-2 cell lines. Compounds 9 20 most cytotoxic, with IC50 values cells ranging from 2.53 to 7.54 µM. Additionally, compounds also found be slightly more than indirubin 2.2-2.7-fold higher cytotoxicity cells. CDK-2 CDK-4 enzyme inhibition assay showed that compound had a inhibitory effect (4.8-fold) comparable CDK-4. Moreover, displayed nanomolar action both EGFR VFGFR-2 enzyme, which around 8.8- 5.4-fold indirubin. induced cycle arrest at G1 phase on HepG2 levels key apoptotic proteins assessed revealed elevated Bax/Bcl-2 ratio, in turn initiated caspase3/7 cascade led activation intrinsic extrinsic pathways. p53 p21 significantly upregulated upon treatment 20. docking results exhibits stronger binding affinity indirubin, similar mode sorafenib VEGFR-2.

Language: Английский

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