Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation
Syed Nazreena✉, Abdulraheem S. A. Almalkib, Serag Eldin I. Elbehairic d, Ali Abdullah Shatid, Mohammad Yahya Alfaifid, Ahmed A. Elhenawya e, Nawaf I. Alsenania, Anas Alfarsia, A. Alhadhramib, Esam A. Alqurashia, Mohammad Mahboob Alama✉
- aDepartment of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Saudi Arabia
- bDepartment of Chemistry, Faculty of Science, Taif University, Taif 21974, Saudi Arabia
- cCell Culture Laboratory, Egyptian Organization for Biological Products and Vaccines, VACSERA Holding Company, Giza 2311, Egypt
- dDepartment of Biology, Faculty of Science, King Khalid University, Abha 61421, Saudi Arabia
- eChemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
- ✉Corresponding author
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Abstract
In the current study, new benzimidazole-based 1,3,4-oxadiazole derivatives have been synthesized and characterized by NMR, IR, MS, and elemental analysis. The final compounds were screened for cytotoxicity against MDA-MB-231, SKOV3, and A549 cell lines and EGFR for inhibitory activities. Compounds 10 and 13 were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC50 0.33 and 0.38 μM, respectively, comparable to erlotinib (IC50 0.39 μM). Furthermore, these two compounds effectively suppressed cell cycle progression and induced cell apoptosis in MDA-MB-231, SKOV3, and A549 cell lines. The docking studies revealed that these compounds showed interactions similar to erlotinib at the EGFR site. It can be concluded that the synthesized molecules effectively inhibit EGFR, can arrest the cell cycle, and may trigger apoptosis and therefore, could be used as lead molecules in the development of new anticancer agents targeting EGFR kinase.