Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations.
In: Journal of Enzyme Inhibition & Medicinal Chemistry, Jg. 38 (2023-12-01), Heft 1, S. 1-21
Online
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
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Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations.
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Autor/in / Beteiligte Person: | Haffez, Hesham ; Elsayed, Nosaiba A. ; Ahmed, Marwa F. ; Fatahala, Samar S. ; Khaleel, Eman F. ; Badi, Rehab Mustafa ; Elkaeed, Eslam B. ; El Hassab, Mahmoud A. ; Hammad, Sherif F. ; Eldehna, Wagdy M. ; Masurier, Nicolas ; El-Haggar, Radwan |
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Zeitschrift: | Journal of Enzyme Inhibition & Medicinal Chemistry, Jg. 38 (2023-12-01), Heft 1, S. 1-21 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 1475-6366 (print) |
DOI: | 10.1080/14756366.2023.2278022 |
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