Targeting CDK2 Kinase in Breast Cancer Employing Novel Oxindole-Quinazoline Conjugates: Design, Synthesis, Biological Assessments and Molecular Docking Study

Syam, Yasmin; Abdelmohsen, Heba; Abdel-Karim, Somia

doi:10.21608/ejchem.2024.329077.10650

Targeting CDK2 Kinase in Breast Cancer Employing Novel Oxindole-Quinazoline Conjugates: Design, Synthesis, Biological Assessments and Molecular Docking Study

Document Type : Original Article

Authors

¹ Department of Therapeutic Chemistry, National Research Centre, Dokki, Cairo, Egypt

² Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Giza 12622, Egypt

³ Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, Egypt

10.21608/ejchem.2024.329077.10650

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.

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