Design, synthesis, biological evaluation and in silico studies of 2-anilino- 4-(benzimidazol- 1-yl)pyrimidine scaffold as antitumor agents
Abstract In an attempt to rationalize the search for new potential Chemotherapeutic agents, a new series of 2-anilinobenzimidazol derivatives with CDK activity have been synthesized. The newly synthesized compounds have been assessed for their cytotoxic effects and CDK activity. These presented comp...
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| Format: | Article |
| Language: | English |
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Springer
2025-05-01
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| Series: | Saudi Pharmaceutical Journal |
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| Online Access: | https://doi.org/10.1007/s44446-025-00010-w |
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| author | Lamees S. Al-Rasheed Siddique Akber Ansari Hanadi H. Asiri Ahmed H. Bakheit Abdulrahman A. Al-mehizia Amsha S. Alsegiani Hamad M. Alkahtani |
| author_facet | Lamees S. Al-Rasheed Siddique Akber Ansari Hanadi H. Asiri Ahmed H. Bakheit Abdulrahman A. Al-mehizia Amsha S. Alsegiani Hamad M. Alkahtani |
| author_sort | Lamees S. Al-Rasheed |
| collection | DOAJ |
| description | Abstract In an attempt to rationalize the search for new potential Chemotherapeutic agents, a new series of 2-anilinobenzimidazol derivatives with CDK activity have been synthesized. The newly synthesized compounds have been assessed for their cytotoxic effects and CDK activity. These presented compounds showed strong inhibition of cell proliferation in various solid cancer cell lines, suggesting a promising approach for treating malignant tumors. Compounds 4 g, 4j, 4 m, and 4q displayed remarkably strong anticancer potencies against HepG2 cells, with IC50 of 7.59, 8.54, 3.56 and 5.88 µM, respectively, compared to the positive control, DOX (IC50 = 4.50 µM). while compound 4 m, and 4q had the highest anticancer activity against HeLa cells, with an IC50 of 6.39 and 9.71 µM, respectively, compared to the positive control DOX (IC50 = 5.57 µM). On the other hand, comparison of IC50 values against MCF-7 cells revealed that compounds 4 g, 4 m, and 4q showed significant anticancer potency with IC50 of 5.08, 2.18 and 8.19 µM, respectively compared to that of the positive control DOX (IC50 = 4.17 µM). Moreover, compound 4 m and 4q were the most potent CDK9 and CDK12 inhibitors. Furthermore, a molecular docking simulation were performed to explore the ability of compounds 4 m to adopt the common binding pattern of CDK9 and CDK12/T1 inhibitors. In silico ADMET results showed that all compounds have favourable drug-like properties since they met Lipinski’s rule of five criteria. Overall, the synthesized anilinopyrimidine derivatives exhibit significant potential as chemotherapeutic agents. |
| format | Article |
| id | doaj-art-dfbf4b5817284ca5803df2824cff9fff |
| institution | Kabale University |
| issn | 1319-0164 2213-7475 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj-art-dfbf4b5817284ca5803df2824cff9fff2025-08-20T03:42:48ZengSpringerSaudi Pharmaceutical Journal1319-01642213-74752025-05-0133311710.1007/s44446-025-00010-wDesign, synthesis, biological evaluation and in silico studies of 2-anilino- 4-(benzimidazol- 1-yl)pyrimidine scaffold as antitumor agentsLamees S. Al-Rasheed0Siddique Akber Ansari1Hanadi H. Asiri2Ahmed H. Bakheit3Abdulrahman A. Al-mehizia4Amsha S. Alsegiani5Hamad M. Alkahtani6Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDrug Exploration and Development (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityAbstract In an attempt to rationalize the search for new potential Chemotherapeutic agents, a new series of 2-anilinobenzimidazol derivatives with CDK activity have been synthesized. The newly synthesized compounds have been assessed for their cytotoxic effects and CDK activity. These presented compounds showed strong inhibition of cell proliferation in various solid cancer cell lines, suggesting a promising approach for treating malignant tumors. Compounds 4 g, 4j, 4 m, and 4q displayed remarkably strong anticancer potencies against HepG2 cells, with IC50 of 7.59, 8.54, 3.56 and 5.88 µM, respectively, compared to the positive control, DOX (IC50 = 4.50 µM). while compound 4 m, and 4q had the highest anticancer activity against HeLa cells, with an IC50 of 6.39 and 9.71 µM, respectively, compared to the positive control DOX (IC50 = 5.57 µM). On the other hand, comparison of IC50 values against MCF-7 cells revealed that compounds 4 g, 4 m, and 4q showed significant anticancer potency with IC50 of 5.08, 2.18 and 8.19 µM, respectively compared to that of the positive control DOX (IC50 = 4.17 µM). Moreover, compound 4 m and 4q were the most potent CDK9 and CDK12 inhibitors. Furthermore, a molecular docking simulation were performed to explore the ability of compounds 4 m to adopt the common binding pattern of CDK9 and CDK12/T1 inhibitors. In silico ADMET results showed that all compounds have favourable drug-like properties since they met Lipinski’s rule of five criteria. Overall, the synthesized anilinopyrimidine derivatives exhibit significant potential as chemotherapeutic agents.https://doi.org/10.1007/s44446-025-00010-wCancerBenzimidazoleCDKAntitumor activityMolecular docking |
| spellingShingle | Lamees S. Al-Rasheed Siddique Akber Ansari Hanadi H. Asiri Ahmed H. Bakheit Abdulrahman A. Al-mehizia Amsha S. Alsegiani Hamad M. Alkahtani Design, synthesis, biological evaluation and in silico studies of 2-anilino- 4-(benzimidazol- 1-yl)pyrimidine scaffold as antitumor agents Saudi Pharmaceutical Journal Cancer Benzimidazole CDK Antitumor activity Molecular docking |
| title | Design, synthesis, biological evaluation and in silico studies of 2-anilino- 4-(benzimidazol- 1-yl)pyrimidine scaffold as antitumor agents |
| title_full | Design, synthesis, biological evaluation and in silico studies of 2-anilino- 4-(benzimidazol- 1-yl)pyrimidine scaffold as antitumor agents |
| title_fullStr | Design, synthesis, biological evaluation and in silico studies of 2-anilino- 4-(benzimidazol- 1-yl)pyrimidine scaffold as antitumor agents |
| title_full_unstemmed | Design, synthesis, biological evaluation and in silico studies of 2-anilino- 4-(benzimidazol- 1-yl)pyrimidine scaffold as antitumor agents |
| title_short | Design, synthesis, biological evaluation and in silico studies of 2-anilino- 4-(benzimidazol- 1-yl)pyrimidine scaffold as antitumor agents |
| title_sort | design synthesis biological evaluation and in silico studies of 2 anilino 4 benzimidazol 1 yl pyrimidine scaffold as antitumor agents |
| topic | Cancer Benzimidazole CDK Antitumor activity Molecular docking |
| url | https://doi.org/10.1007/s44446-025-00010-w |
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