Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation
In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, and 13a) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2103552 |
| _version_ | 1811312990432002048 |
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| author | Mohammed S. Taghour Hazem A. Mahdy Maher H. Gomaa Ahmed Aglan Mahmoud Gomaa Eldeib Alaa Elwan Mohammed A. Dahab Eslam B. Elkaeed Aisha A. Alsfouk Mohamed M. Khalifa Ibrahim H. Eissa Hazem Elkady |
| author_facet | Mohammed S. Taghour Hazem A. Mahdy Maher H. Gomaa Ahmed Aglan Mahmoud Gomaa Eldeib Alaa Elwan Mohammed A. Dahab Eslam B. Elkaeed Aisha A. Alsfouk Mohamed M. Khalifa Ibrahim H. Eissa Hazem Elkady |
| author_sort | Mohammed S. Taghour |
| collection | DOAJ |
| description | In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, and 13a) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member 12 l (IC50 = 10.50 μM and 15.21 μM against HepG2 and MCF-7, respectively) had the most promising VEGFR-2 inhibitory activity (IC50 = 97.38 nM). A further biological evaluation revealed that compound 12l could arrest the HepG2 cell growth mainly at the Pre-G1 and G1 phases. Furthermore, compound 12l could induce apoptosis in HepG2 cells by 35.13%. likely, compound 12l exhibited a significant elevation in caspase-3 level (2.98-fold) and BAX (3.40-fold), and a significant reduction in Bcl-2 level (2.12-fold). Finally, docking studies indicated that 12l exhibited interactions with the key amino acids in a similar way to sorafenib. |
| first_indexed | 2024-04-13T10:46:21Z |
| format | Article |
| id | doaj.art-f180310e302d49f29cd0dbeea3e88d77 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-13T10:46:21Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-f180310e302d49f29cd0dbeea3e88d772022-12-22T02:49:47ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712063207710.1080/14756366.2022.2103552Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluationMohammed S. Taghour0Hazem A. Mahdy1Maher H. Gomaa2Ahmed Aglan3Mahmoud Gomaa Eldeib4Alaa Elwan5Mohammed A. Dahab6Eslam B. Elkaeed7Aisha A. Alsfouk8Mohamed M. Khalifa9Ibrahim H. Eissa10Hazem Elkady11Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptBiochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptBiochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptBiochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptIn this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, and 13a) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member 12 l (IC50 = 10.50 μM and 15.21 μM against HepG2 and MCF-7, respectively) had the most promising VEGFR-2 inhibitory activity (IC50 = 97.38 nM). A further biological evaluation revealed that compound 12l could arrest the HepG2 cell growth mainly at the Pre-G1 and G1 phases. Furthermore, compound 12l could induce apoptosis in HepG2 cells by 35.13%. likely, compound 12l exhibited a significant elevation in caspase-3 level (2.98-fold) and BAX (3.40-fold), and a significant reduction in Bcl-2 level (2.12-fold). Finally, docking studies indicated that 12l exhibited interactions with the key amino acids in a similar way to sorafenib.https://www.tandfonline.com/doi/10.1080/14756366.2022.2103552Anticancercell cycleapoptosisbenzoxazoleVEGFR-2 |
| spellingShingle | Mohammed S. Taghour Hazem A. Mahdy Maher H. Gomaa Ahmed Aglan Mahmoud Gomaa Eldeib Alaa Elwan Mohammed A. Dahab Eslam B. Elkaeed Aisha A. Alsfouk Mohamed M. Khalifa Ibrahim H. Eissa Hazem Elkady Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation Journal of Enzyme Inhibition and Medicinal Chemistry Anticancer cell cycle apoptosis benzoxazole VEGFR-2 |
| title | Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation |
| title_full | Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation |
| title_fullStr | Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation |
| title_full_unstemmed | Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation |
| title_short | Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation |
| title_sort | benzoxazole derivatives as new vegfr 2 inhibitors and apoptosis inducers design synthesis in silico studies and antiproliferative evaluation |
| topic | Anticancer cell cycle apoptosis benzoxazole VEGFR-2 |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2103552 |
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