Aminopyridone-Linked Benzimidazoles: A Fragment-Based Drug Design for the Development of CDK9 Inhibitors

• DOI: 10.4155/fmc-2023-0139
• Publication Date: 2023-08-16T08:44:26Z
• Authors: Ebtehal M Husseiny; Hamada S Abulkhair; Sanadelaslam SA E...; Nada Osama; Mona S El-Zoghbi
• Keywords: Structure-Activity Relationship; Molecular Structure; Cell Line, Tumor; Drug Design; MCF-7 Cells; Humans; Antineoplastic Agents; Benzimidazoles; Drug Screening Assays, Antitumor; Cyclin-Dependent Kinase 9; 3. Good health; Cell Proliferation

Aim: A fragment-based design and synthesis of three novel series aminopyridone-linked benzimidazoles as potential anticancer candidates with significant CDK9 inhibition was implemented. Materials & methods: All synthesized compounds were submitted to National Cancer Institute, 60 cell lines seven-dose cytotoxicity toward cancer cells. Results: Compounds 2, 4a, 4c, 4d, 6a 8a exhibited selectivity IC 50 range 7.61–57.75 μM. Regarding the mechanism either in vitro or silico, displayed potent value 0.424–8.461 Compound arrested cycle at S phase induced apoptosis MCF-7 Conclusion: is a promising inhibitor that warrants additional research for treatment.