Targeting CDK2 Kinase in Breast Cancer Employing Novel Oxindole-Quinazoline Conjugates: Design, Synthesis, Biological Assessments and Molecular Docking Study | ||||
| Egyptian Journal of Chemistry | ||||
| Volume 68, Issue 7, July 2025, Page 569-579 PDF (914.06 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ejchem.2024.329077.10650 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Yasmin Syam  1; Heba Abdelmohsen2; Somia Abdel-Karim3
| ||||
| 1Department of Therapeutic Chemistry, National Research Centre, Dokki, Cairo, Egypt | ||||
| 2Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Giza 12622, Egypt | ||||
| 3Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, Egypt | ||||
| Abstract | ||||
| This study involved the design and synthesis of a novel series of oxindole-quinazoline hybrids targeting CDK2 in breast cancer. MTT assay investigated the cytotoxic activity of all the synthesized compounds 8a-e towards MCF-7 breast adenocarcinoma with IC50 ranging from 0.007 to 0.104 µM. The most active compound 8a was also evaluated for its cytotoxic activity on normal breast epithelial cell line MCF-10a cell line. The hybrid 8a demonstrated a high safety margin with SI = 10.57. Further assessment of 8a on its inhibitory activity on CDK2 proved its optimum potency with IC50 = 0.011 nM. Molecular docking of 8a in the binding pocket of CDK2 proved the expected binding mode. | ||||
| Keywords | ||||
| oxindole-quinazoline hybrids, breast cancer; CDK-2 inhibitors; molecular docking | ||||
|
Statistics Article View: 277 PDF Download: 26 |
||||
