1-Benzyl-5-bromo-3-hydrazonoindolin-2-ones as Novel Anticancer Agents: Synthesis, Biological Evaluation and Molecular Modeling Insights.
Al-Warhi, T
Almahli, H
Maklad, RM
Elsayed, ZM
El Hassab, MA
Alotaibi, OJ
Aljaeed, N
Ayyad, RR
Ghabour, HA
Eldehna, WM
El-Ashrey, MK
- Publisher:
- MDPI
- Publication Type:
- Journal Article
- Citation:
- Molecules, 2023, 28, (7), pp. 3203
- Issue Date:
- 2023-04-04
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Al-Warhi, T | |
dc.contributor.author | Almahli, H | |
dc.contributor.author | Maklad, RM | |
dc.contributor.author | Elsayed, ZM | |
dc.contributor.author | El Hassab, MA | |
dc.contributor.author | Alotaibi, OJ | |
dc.contributor.author | Aljaeed, N | |
dc.contributor.author | Ayyad, RR | |
dc.contributor.author | Ghabour, HA | |
dc.contributor.author | Eldehna, WM | |
dc.contributor.author | El-Ashrey, MK | |
dc.date.accessioned | 2025-01-31T01:18:46Z | |
dc.date.available | 2023-03-26 | |
dc.date.available | 2025-01-31T01:18:46Z | |
dc.date.issued | 2023-04-04 | |
dc.identifier.citation | Molecules, 2023, 28, (7), pp. 3203 | |
dc.identifier.issn | 1420-3049 | |
dc.identifier.issn | 1420-3049 | |
dc.identifier.uri | http://hdl.handle.net/10453/184734 | |
dc.description.abstract | Human health is experiencing several obstacles in the modern medical era, particularly cancer. As a result, the cancer therapeutic arsenal should be continually expanded with innovative small molecules that preferentially target tumour cells. In this study, we describe the development of two small molecule series (7a-d and 12a-e) based on the 1-benzyl-5-bromoindolin-2-one scaffold that connected through a hydrazone linker to a 4-arylthiazole (7a-d) or 4-methyl-5-(aryldiazenyl)thiazole (12a-e) moiety. The anticancer activity of all the reported indolin-2-one derivatives was assessed against breast (MCF-7) and lung (A-549) cancer cell lines. The 4-arylthiazole-bearing derivatives 7c and 7d revealed the best anticancer activity toward MCF-7 cells (IC50 = 7.17 ± 0.94 and 2.93 ± 0.47, respectively). Furthermore, the VEGFR-2 inhibitory activity for 7c and 7d was evaluated. Both molecules disclosed good inhibitory activity, and their IC50 values were equal to 0.728 µM and 0.503 µM, respectively. Additionally, the impacts of 7d on the cell cycle phases as well as on the levels of different apoptotic markers (caspase-3, caspase-9, Bax, and Bcl-2) were assessed. Molecular docking and dynamic simulations are carried out to explore the binding mode of 7d within the VEGFR-2 active site. | |
dc.format | Electronic | |
dc.language | eng | |
dc.publisher | MDPI | |
dc.relation.ispartof | Molecules | |
dc.relation.isbasedon | 10.3390/molecules28073203 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 0307 Theoretical and Computational Chemistry | |
dc.subject.classification | Organic Chemistry | |
dc.subject.classification | 3404 Medicinal and biomolecular chemistry | |
dc.subject.classification | 3405 Organic chemistry | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Molecular Structure | |
dc.subject.mesh | Structure-Activity Relationship | |
dc.subject.mesh | Vascular Endothelial Growth Factor Receptor-2 | |
dc.subject.mesh | Molecular Docking Simulation | |
dc.subject.mesh | Cell Proliferation | |
dc.subject.mesh | Antineoplastic Agents | |
dc.subject.mesh | MCF-7 Cells | |
dc.subject.mesh | Drug Screening Assays, Antitumor | |
dc.subject.mesh | Protein Kinase Inhibitors | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Vascular Endothelial Growth Factor Receptor-2 | |
dc.subject.mesh | Antineoplastic Agents | |
dc.subject.mesh | Protein Kinase Inhibitors | |
dc.subject.mesh | Drug Screening Assays, Antitumor | |
dc.subject.mesh | Cell Proliferation | |
dc.subject.mesh | Molecular Structure | |
dc.subject.mesh | Structure-Activity Relationship | |
dc.subject.mesh | MCF-7 Cells | |
dc.subject.mesh | Molecular Docking Simulation | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Molecular Structure | |
dc.subject.mesh | Structure-Activity Relationship | |
dc.subject.mesh | Vascular Endothelial Growth Factor Receptor-2 | |
dc.subject.mesh | Molecular Docking Simulation | |
dc.subject.mesh | Cell Proliferation | |
dc.subject.mesh | Antineoplastic Agents | |
dc.subject.mesh | MCF-7 Cells | |
dc.subject.mesh | Drug Screening Assays, Antitumor | |
dc.subject.mesh | Protein Kinase Inhibitors | |
dc.title | 1-Benzyl-5-bromo-3-hydrazonoindolin-2-ones as Novel Anticancer Agents: Synthesis, Biological Evaluation and Molecular Modeling Insights. | |
dc.type | Journal Article | |
utslib.citation.volume | 28 | |
utslib.location.activity | Switzerland | |
utslib.for | 0304 Medicinal and Biomolecular Chemistry | |
utslib.for | 0305 Organic Chemistry | |
utslib.for | 0307 Theoretical and Computational Chemistry | |
pubs.organisational-group | University of Technology Sydney | |
pubs.organisational-group | University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences | |
utslib.copyright.status | open_access | * |
dc.rights.license | This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/ | |
dc.date.updated | 2025-01-31T01:18:43Z | |
pubs.issue | 7 | |
pubs.publication-status | Published online | |
pubs.volume | 28 | |
utslib.citation.issue | 7 |
Abstract:
Human health is experiencing several obstacles in the modern medical era, particularly cancer. As a result, the cancer therapeutic arsenal should be continually expanded with innovative small molecules that preferentially target tumour cells. In this study, we describe the development of two small molecule series (7a-d and 12a-e) based on the 1-benzyl-5-bromoindolin-2-one scaffold that connected through a hydrazone linker to a 4-arylthiazole (7a-d) or 4-methyl-5-(aryldiazenyl)thiazole (12a-e) moiety. The anticancer activity of all the reported indolin-2-one derivatives was assessed against breast (MCF-7) and lung (A-549) cancer cell lines. The 4-arylthiazole-bearing derivatives 7c and 7d revealed the best anticancer activity toward MCF-7 cells (IC50 = 7.17 ± 0.94 and 2.93 ± 0.47, respectively). Furthermore, the VEGFR-2 inhibitory activity for 7c and 7d was evaluated. Both molecules disclosed good inhibitory activity, and their IC50 values were equal to 0.728 µM and 0.503 µM, respectively. Additionally, the impacts of 7d on the cell cycle phases as well as on the levels of different apoptotic markers (caspase-3, caspase-9, Bax, and Bcl-2) were assessed. Molecular docking and dynamic simulations are carried out to explore the binding mode of 7d within the VEGFR-2 active site.
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