Targeting CDK2 Kinase in Breast Cancer Employing Novel Oxindole-Quinazoline Conjugates: Design, Synthesis, Biological Assessments and Molecular Docking Study | ||
| Egyptian Journal of Chemistry | ||
| Articles in Press, Accepted Manuscript, Available Online from 03 December 2024 | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejchem.2024.329077.10650 | ||
| 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 | ||
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