Synthesis, molecular modeling and bioactivity of new bis-thiazole, thiazole-pyrazole, and thiazole-pyridine analogues
Several new thiazole derivatives linked pyrazole and/or pyridine rings were synthesized based on the versatile precursor 2-(5-acetyl-4-methyl-3-phenylthiazol-2(3H)-ylidene)acetonitrile (1). The synthesized derivatives were optimized using DFT approach in order to inspect the configurations and energ...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Journal of Saudi Chemical Society |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319610323001588 |
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| author | Abrar Bayazeed Rua B. Alnoman Kahdr Alatawi Omar M. Alatawi Alaa M. Alqahtani Mariam Mojally Noof A. Alenazi Nashwa M. El-Metwaly |
| author_facet | Abrar Bayazeed Rua B. Alnoman Kahdr Alatawi Omar M. Alatawi Alaa M. Alqahtani Mariam Mojally Noof A. Alenazi Nashwa M. El-Metwaly |
| author_sort | Abrar Bayazeed |
| collection | DOAJ |
| description | Several new thiazole derivatives linked pyrazole and/or pyridine rings were synthesized based on the versatile precursor 2-(5-acetyl-4-methyl-3-phenylthiazol-2(3H)-ylidene)acetonitrile (1). The synthesized derivatives were optimized using DFT approach in order to inspect the configurations and energies of the HOMO-LUMO orbitals. The data disclosed low energy gap (ΔEH-L), 0.99–2.54 eV, following the order 9 < 3 = 4 ≈ 2 ≈ 8 < 5 < 1 < 7 ≈ 6. The in vitro anticancer activity of the new thiazole hybrids was tested against three cancer cell lines (HepG2, HCT-116, and MCF-7) as well as standard fibroblast cells (WI38) using Doxorubicin as a reference drug. The thiazole-pyridine hybrids 8 and 9 exhibited high cytotoxic efficacies against the MCF-7 cell line, IC50 28.53 ± 0.39 and 25.47 ± 0.54 µM. Moreover, the synthesized hybrids were docked against the crystal structure of (PDB: 3rcd) as a representative protein for the human epidermal growth factor receptor (HER2) to approve the relationship between the in vitro cytotoxicity results and inhibitor binding interactions. The docking study showed that thiazole-pyridine hybrids 8 and 9 displayed the highest score of bindings, which was compatible with the results of the cytotoxicity results. |
| first_indexed | 2024-03-08T20:11:50Z |
| format | Article |
| id | doaj.art-26e69a90e5d2492b9a7fcc241ece580a |
| institution | Directory Open Access Journal |
| issn | 1319-6103 |
| language | English |
| last_indexed | 2024-03-08T20:11:50Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Saudi Chemical Society |
| spelling | doaj.art-26e69a90e5d2492b9a7fcc241ece580a2023-12-23T05:20:11ZengElsevierJournal of Saudi Chemical Society1319-61032023-11-01276101754Synthesis, molecular modeling and bioactivity of new bis-thiazole, thiazole-pyrazole, and thiazole-pyridine analoguesAbrar Bayazeed0Rua B. Alnoman1Kahdr Alatawi2Omar M. Alatawi3Alaa M. Alqahtani4Mariam Mojally5Noof A. Alenazi6Nashwa M. El-Metwaly7Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah 24230, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Madinah, P.O. Box 344, Saudi ArabiaPharmaceuticals Chemistry Department, Faculty of Clinical Pharmacy, Al-Baha University, Al Baha 65779, Saudi ArabiaDepartment of Chemistry, Faculty of Science, University of Tabuk, Tabuk 47512, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi ArabiaDepartment of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; Corresponding author.Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah 24230, Saudi Arabia; Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhoria Street, 35516, EgyptSeveral new thiazole derivatives linked pyrazole and/or pyridine rings were synthesized based on the versatile precursor 2-(5-acetyl-4-methyl-3-phenylthiazol-2(3H)-ylidene)acetonitrile (1). The synthesized derivatives were optimized using DFT approach in order to inspect the configurations and energies of the HOMO-LUMO orbitals. The data disclosed low energy gap (ΔEH-L), 0.99–2.54 eV, following the order 9 < 3 = 4 ≈ 2 ≈ 8 < 5 < 1 < 7 ≈ 6. The in vitro anticancer activity of the new thiazole hybrids was tested against three cancer cell lines (HepG2, HCT-116, and MCF-7) as well as standard fibroblast cells (WI38) using Doxorubicin as a reference drug. The thiazole-pyridine hybrids 8 and 9 exhibited high cytotoxic efficacies against the MCF-7 cell line, IC50 28.53 ± 0.39 and 25.47 ± 0.54 µM. Moreover, the synthesized hybrids were docked against the crystal structure of (PDB: 3rcd) as a representative protein for the human epidermal growth factor receptor (HER2) to approve the relationship between the in vitro cytotoxicity results and inhibitor binding interactions. The docking study showed that thiazole-pyridine hybrids 8 and 9 displayed the highest score of bindings, which was compatible with the results of the cytotoxicity results.http://www.sciencedirect.com/science/article/pii/S1319610323001588Thiazole derivativesDFT optimizationAnticancer activityMolecular docking |
| spellingShingle | Abrar Bayazeed Rua B. Alnoman Kahdr Alatawi Omar M. Alatawi Alaa M. Alqahtani Mariam Mojally Noof A. Alenazi Nashwa M. El-Metwaly Synthesis, molecular modeling and bioactivity of new bis-thiazole, thiazole-pyrazole, and thiazole-pyridine analogues Journal of Saudi Chemical Society Thiazole derivatives DFT optimization Anticancer activity Molecular docking |
| title | Synthesis, molecular modeling and bioactivity of new bis-thiazole, thiazole-pyrazole, and thiazole-pyridine analogues |
| title_full | Synthesis, molecular modeling and bioactivity of new bis-thiazole, thiazole-pyrazole, and thiazole-pyridine analogues |
| title_fullStr | Synthesis, molecular modeling and bioactivity of new bis-thiazole, thiazole-pyrazole, and thiazole-pyridine analogues |
| title_full_unstemmed | Synthesis, molecular modeling and bioactivity of new bis-thiazole, thiazole-pyrazole, and thiazole-pyridine analogues |
| title_short | Synthesis, molecular modeling and bioactivity of new bis-thiazole, thiazole-pyrazole, and thiazole-pyridine analogues |
| title_sort | synthesis molecular modeling and bioactivity of new bis thiazole thiazole pyrazole and thiazole pyridine analogues |
| topic | Thiazole derivatives DFT optimization Anticancer activity Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S1319610323001588 |
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