Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation
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 &...
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MDPI AG
2022-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/20/6899 |
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| author | Syed Nazreen Abdulraheem S. A. Almalki Serag Eldin I. Elbehairi Ali A. Shati Mohammad Y. Alfaifi Ahmed A. Elhenawy Nawaf I. Alsenani Anas Alfarsi Abdulrahman Alhadhrami Esam A. Alqurashi Mohammad Mahboob Alam |
| author_facet | Syed Nazreen Abdulraheem S. A. Almalki Serag Eldin I. Elbehairi Ali A. Shati Mohammad Y. Alfaifi Ahmed A. Elhenawy Nawaf I. Alsenani Anas Alfarsi Abdulrahman Alhadhrami Esam A. Alqurashi Mohammad Mahboob Alam |
| author_sort | Syed Nazreen |
| collection | DOAJ |
| description | 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 <b>10</b> and <b>13</b> were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC<sub>50</sub> 0.33 and 0.38 μM, respectively, comparable to erlotinib (IC<sub>50</sub> 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. |
| first_indexed | 2024-03-09T19:42:41Z |
| format | Article |
| id | doaj.art-b5e0884dba2e4d2d8776ea9257b6f0f5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T19:42:41Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b5e0884dba2e4d2d8776ea9257b6f0f52023-11-24T01:33:28ZengMDPI AGMolecules1420-30492022-10-012720689910.3390/molecules27206899Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological EvaluationSyed Nazreen0Abdulraheem S. A. Almalki1Serag Eldin I. Elbehairi2Ali A. Shati3Mohammad Y. Alfaifi4Ahmed A. Elhenawy5Nawaf I. Alsenani6Anas Alfarsi7Abdulrahman Alhadhrami8Esam A. Alqurashi9Mohammad Mahboob Alam10Department of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Taif University, Taif 21974, Saudi ArabiaDepartment of Biology, Faculty of Science, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Biology, Faculty of Science, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Biology, Faculty of Science, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Taif University, Taif 21974, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Saudi ArabiaIn 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 <b>10</b> and <b>13</b> were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC<sub>50</sub> 0.33 and 0.38 μM, respectively, comparable to erlotinib (IC<sub>50</sub> 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.https://www.mdpi.com/1420-3049/27/20/68991,3,4-oxadiazolebenzimidazolecell cycle arrestapoptosisdocking |
| spellingShingle | Syed Nazreen Abdulraheem S. A. Almalki Serag Eldin I. Elbehairi Ali A. Shati Mohammad Y. Alfaifi Ahmed A. Elhenawy Nawaf I. Alsenani Anas Alfarsi Abdulrahman Alhadhrami Esam A. Alqurashi Mohammad Mahboob Alam Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation Molecules 1,3,4-oxadiazole benzimidazole cell cycle arrest apoptosis docking |
| title | Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation |
| title_full | Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation |
| title_fullStr | Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation |
| title_full_unstemmed | Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation |
| title_short | Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation |
| title_sort | cell cycle arrest and apoptosis inducing ability of benzimidazole derivatives design synthesis docking and biological evaluation |
| topic | 1,3,4-oxadiazole benzimidazole cell cycle arrest apoptosis docking |
| url | https://www.mdpi.com/1420-3049/27/20/6899 |
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