Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors : synthesis, biological evaluations, and molecular dynamic simulations
Significant advancements have been made in the domain of targeted anticancer therapy for the management of malignancies in recent times. VEGFR-2 is characterised by its pivotal involvement in angiogenesis and subsequent mechanisms that promote tumour cells survival. Herein, novel N-arylmethyl-aniline/chalcone hybrids 5a-5n were designed and synthesised as potential anticancer and VEGFR-2 inhibitors. The anticancer activity was evaluated at the NCI-USA, resulting in the identification of 10 remarkably potent molecules 5a-5j that were further subjected to the five-dose assays. Thereafter, they were explored for their VEGFR-2 inhibitory activity where 5e and 5h emerged as the most potent inhibitors. 5e and 5h induced apoptosis with cell cycle arrest at the SubG0-G1 phase within HCT-116 cells. Moreover, their impact on some key apoptotic genes was assessed, suggesting caspase-dependent apoptosis. Furthermore, molecular docking and molecular dynamics simulations were conducted to explore the binding modes and stability of the protein-ligand complexes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Journal of enzyme inhibition and medicinal chemistry - 38(2023), 1 vom: 01. Dez., Seite 2278022 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Haffez, Hesham [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.11.2023 Date Revised 11.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/14756366.2023.2278022 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Significant advancements have been made in the domain of targeted anticancer therapy for the management of malignancies in recent times. VEGFR-2 is characterised by its pivotal involvement in angiogenesis and subsequent mechanisms that promote tumour cells survival. Herein, novel N-arylmethyl-aniline/chalcone hybrids 5a-5n were designed and synthesised as potential anticancer and VEGFR-2 inhibitors. The anticancer activity was evaluated at the NCI-USA, resulting in the identification of 10 remarkably potent molecules 5a-5j that were further subjected to the five-dose assays. Thereafter, they were explored for their VEGFR-2 inhibitory activity where 5e and 5h emerged as the most potent inhibitors. 5e and 5h induced apoptosis with cell cycle arrest at the SubG0-G1 phase within HCT-116 cells. Moreover, their impact on some key apoptotic genes was assessed, suggesting caspase-dependent apoptosis. Furthermore, molecular docking and molecular dynamics simulations were conducted to explore the binding modes and stability of the protein-ligand complexes | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Ahmed, Marwa F |e verfasserin |4 aut | |
| 700 | 1 | |a Fatahala, Samar S |e verfasserin |4 aut | |
| 700 | 1 | |a Khaleel, Eman F |e verfasserin |4 aut | |
| 700 | 1 | |a Badi, Rehab Mustafa |e verfasserin |4 aut | |
| 700 | 1 | |a Elkaeed, Eslam B |e verfasserin |4 aut | |
| 700 | 1 | |a El Hassab, Mahmoud A |e verfasserin |4 aut | |
| 700 | 1 | |a Hammad, Sherif F |e verfasserin |4 aut | |
| 700 | 1 | |a Eldehna, Wagdy M |e verfasserin |4 aut | |
| 700 | 1 | |a Masurier, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a El-Haggar, Radwan |e verfasserin |4 aut | |
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