Novel thiazolyl-pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation, and molecular docking studies
We synthesized and spectroscopically confirmed a series of 1,3-thiazolyl-pyrimidine derivatives to investigate their potential role in cancer therapy. These were created by reacting 2-(1-(6-methyl-2-oxo-4-phenyl- 1,2,3,4-tetrahydropyrimidin-5-yl)ethylidene)hydrazine-1-carbothioamide with hydrazonoyl...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624007045 |
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| author | Tariq Z. Abolibda Abdel-Aziz A.A. El-Sayed Basant Farag Magdi E.A. Zaki Abdulwahed Alrehaily Hossein M. Elbadawy Ahmad A. Al-Shahri Saleh R. Alsenani Sobhi M. Gomha |
| author_facet | Tariq Z. Abolibda Abdel-Aziz A.A. El-Sayed Basant Farag Magdi E.A. Zaki Abdulwahed Alrehaily Hossein M. Elbadawy Ahmad A. Al-Shahri Saleh R. Alsenani Sobhi M. Gomha |
| author_sort | Tariq Z. Abolibda |
| collection | DOAJ |
| description | We synthesized and spectroscopically confirmed a series of 1,3-thiazolyl-pyrimidine derivatives to investigate their potential role in cancer therapy. These were created by reacting 2-(1-(6-methyl-2-oxo-4-phenyl- 1,2,3,4-tetrahydropyrimidin-5-yl)ethylidene)hydrazine-1-carbothioamide with hydrazonoyl halides and α-halo compounds, with structures confirmed by spectroscopy. The growth-inhibitory potential of these compounds against HepG2 liver cancer cells was assessed using the MTT assay. Five compounds, namely 8a, 10, 12a, 12b, and 14, exhibited promising anticancer activity with IC50 values of 5.02 ± 1.83, 4.04 ± 1.37, 3.81 ± 1.96, 2.39 ± 0.75, and 3.27 ± 1.13 μM, respectively, all of which were more effective than doxorubicin (IC50 = 6.18 ± 0.29 μM). Molecular docking analyses were conducted to investigate the probable binding conformations of the most potent anticancer agents. The docking studies were in good agreement with the in vitro biological results, revealing that compounds 12b, 14, 12a, 10, and 8a demonstrated strong molecular interactions with protein CK2 α. The compounds may serve as adjuvants in cancer treatment. In silico ADMET studies revealed that the synthesized compounds exhibit favorable oral bioavailability profiles. |
| format | Article |
| id | doaj-art-3bb0e4618f9c47058a98a47abcd52a70 |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-3bb0e4618f9c47058a98a47abcd52a702025-01-29T05:00:54ZengElsevierResults in Chemistry2211-71562025-01-0113102008Novel thiazolyl-pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation, and molecular docking studiesTariq Z. Abolibda0Abdel-Aziz A.A. El-Sayed1Basant Farag2Magdi E.A. Zaki3Abdulwahed Alrehaily4Hossein M. Elbadawy5Ahmad A. Al-Shahri6Saleh R. Alsenani7Sobhi M. Gomha8Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi ArabiaBiology Department, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Zagazig University, Zagazig 44519, EgyptDepartment of Chemistry, Faculty of Science, Imam Mohammed Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia; Corresponding authors.Biology Department, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Jurisprudence of Sunnah and Its Sources, Faculty of the Noble Hadith, Islamic University of Madinah, Madinah 41477, Saudi ArabiaBiology Department, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia; Corresponding authors.We synthesized and spectroscopically confirmed a series of 1,3-thiazolyl-pyrimidine derivatives to investigate their potential role in cancer therapy. These were created by reacting 2-(1-(6-methyl-2-oxo-4-phenyl- 1,2,3,4-tetrahydropyrimidin-5-yl)ethylidene)hydrazine-1-carbothioamide with hydrazonoyl halides and α-halo compounds, with structures confirmed by spectroscopy. The growth-inhibitory potential of these compounds against HepG2 liver cancer cells was assessed using the MTT assay. Five compounds, namely 8a, 10, 12a, 12b, and 14, exhibited promising anticancer activity with IC50 values of 5.02 ± 1.83, 4.04 ± 1.37, 3.81 ± 1.96, 2.39 ± 0.75, and 3.27 ± 1.13 μM, respectively, all of which were more effective than doxorubicin (IC50 = 6.18 ± 0.29 μM). Molecular docking analyses were conducted to investigate the probable binding conformations of the most potent anticancer agents. The docking studies were in good agreement with the in vitro biological results, revealing that compounds 12b, 14, 12a, 10, and 8a demonstrated strong molecular interactions with protein CK2 α. The compounds may serve as adjuvants in cancer treatment. In silico ADMET studies revealed that the synthesized compounds exhibit favorable oral bioavailability profiles.http://www.sciencedirect.com/science/article/pii/S2211715624007045HydrazonothiazolesHydrazonoyl chloridesAnticancer activityMolecular docking studies and in silico studies |
| spellingShingle | Tariq Z. Abolibda Abdel-Aziz A.A. El-Sayed Basant Farag Magdi E.A. Zaki Abdulwahed Alrehaily Hossein M. Elbadawy Ahmad A. Al-Shahri Saleh R. Alsenani Sobhi M. Gomha Novel thiazolyl-pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation, and molecular docking studies Results in Chemistry Hydrazonothiazoles Hydrazonoyl chlorides Anticancer activity Molecular docking studies and in silico studies |
| title | Novel thiazolyl-pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation, and molecular docking studies |
| title_full | Novel thiazolyl-pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation, and molecular docking studies |
| title_fullStr | Novel thiazolyl-pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation, and molecular docking studies |
| title_full_unstemmed | Novel thiazolyl-pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation, and molecular docking studies |
| title_short | Novel thiazolyl-pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation, and molecular docking studies |
| title_sort | novel thiazolyl pyrimidine derivatives as potential anticancer agents synthesis biological evaluation and molecular docking studies |
| topic | Hydrazonothiazoles Hydrazonoyl chlorides Anticancer activity Molecular docking studies and in silico studies |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624007045 |
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