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-anilin...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2278022 |
| _version_ | 1827123355037204480 |
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| author | Hesham Haffez Nosaiba A. Elsayed Marwa F. Ahmed Samar S. Fatahala Eman F. Khaleel Rehab Mustafa Badi Eslam B. Elkaeed Mahmoud A. El Hassab Sherif F. Hammad Wagdy M. Eldehna Nicolas Masurier Radwan El-Haggar |
| author_facet | Hesham Haffez Nosaiba A. Elsayed Marwa F. Ahmed Samar S. Fatahala Eman F. Khaleel Rehab Mustafa Badi Eslam B. Elkaeed Mahmoud A. El Hassab Sherif F. Hammad Wagdy M. Eldehna Nicolas Masurier Radwan El-Haggar |
| author_sort | Hesham Haffez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T02:02:58Z |
| format | Article |
| id | doaj.art-8fcc8ea833f943b4862f2890cfe139e0 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2025-03-20T14:23:36Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-8fcc8ea833f943b4862f2890cfe139e02024-09-09T17:23:20ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2278022Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulationsHesham Haffez0Nosaiba A. Elsayed1Marwa F. Ahmed2Samar S. Fatahala3Eman F. Khaleel4Rehab Mustafa Badi5Eslam B. Elkaeed6Mahmoud A. El Hassab7Sherif F. Hammad8Wagdy M. Eldehna9Nicolas Masurier10Radwan El-Haggar11Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Cairo, Ain Helwan, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Ain Helwan, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Ain Helwan, EgyptPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, EgyptDepartment of Medical Physiology, College of Medicine, King Khalid University, Asir, Saudi ArabiaDepartment of Medical Physiology, College of Medicine, King Khalid University, Asir, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi ArabiaDepartment of Medicinal Chemistry, Faculty of Pharmacy, King Salman International University (KSIU), South Sinai, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Ain Helwan, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, EgyptInstitut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université de Montpellier, ENSCM, Montpellier, FranceDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Ain Helwan, EgyptSignificant 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.https://www.tandfonline.com/doi/10.1080/14756366.2023.2278022VEGFR-2anticancer agentsapoptosis inductionmolecular docking |
| spellingShingle | Hesham Haffez Nosaiba A. Elsayed Marwa F. Ahmed Samar S. Fatahala Eman F. Khaleel Rehab Mustafa Badi Eslam B. Elkaeed Mahmoud A. El Hassab Sherif F. Hammad Wagdy M. Eldehna Nicolas Masurier Radwan El-Haggar Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations Journal of Enzyme Inhibition and Medicinal Chemistry VEGFR-2 anticancer agents apoptosis induction molecular docking |
| title | Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations |
| title_full | Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations |
| title_fullStr | Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations |
| title_full_unstemmed | Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations |
| title_short | Novel N-Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations |
| title_sort | novel n arylmethyl aniline chalcone hybrids as potential vegfr inhibitors synthesis biological evaluations and molecular dynamic simulations |
| topic | VEGFR-2 anticancer agents apoptosis induction molecular docking |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2278022 |
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