Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers
A novel series of 2-thioacetamide linked benzoxazole-benzamide conjugates 1–15 was designed as potential inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The prepared compounds were evaluated for their potential antitumor activity and their corresponding selective cytotoxic...
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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 |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2081844 |
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| author | Ibrahim H. Eissa Radwan El-Haggar Mohammed A. Dahab Marwa F. Ahmed Hazem A. Mahdy Reem I. Alsantali Alaa Elwan Nicolas Masurier Samar S. Fatahala |
| author_facet | Ibrahim H. Eissa Radwan El-Haggar Mohammed A. Dahab Marwa F. Ahmed Hazem A. Mahdy Reem I. Alsantali Alaa Elwan Nicolas Masurier Samar S. Fatahala |
| author_sort | Ibrahim H. Eissa |
| collection | DOAJ |
| description | A novel series of 2-thioacetamide linked benzoxazole-benzamide conjugates 1–15 was designed as potential inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The prepared compounds were evaluated for their potential antitumor activity and their corresponding selective cytotoxicity was estimated using normal human fibroblast (WI-38) cells. Compounds 1, 9–12 and 15 showed good selectivity and displayed excellent cytotoxic activity against both HCT-116 and MCF-7 cancer cell lines compared to sorafenib, used as a reference compound. Furthermore, compounds 1 and 11 showed potent VEGFR-2 inhibitory activity. The cell cycle progression assay showed that 1 and 11 induced cell cycle arrest at G2/M phase, with a concomitant increase in the pre-G1 cell population. Further pharmacological studies showed that 1 and 11 induced apoptosis and inhibited the expression of the anti-apoptotic Bcl-2 and Bcl-xL proteins in both cell lines. Therefore, compounds 1 and 11 might serve as promising candidates for future anticancer therapy development. |
| format | Article |
| id | doaj-art-df00a10607564622a1dbea3897e95ec3 |
| institution | OA Journals |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-df00a10607564622a1dbea3897e95ec32025-08-20T02:10:17ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013711587159910.1080/14756366.2022.2081844Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducersIbrahim H. Eissa0Radwan El-Haggar1Mohammed A. Dahab2Marwa F. Ahmed3Hazem A. Mahdy4Reem I. Alsantali5Alaa Elwan6Nicolas Masurier7Samar S. Fatahala8Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptPharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, EgyptPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptPharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, EgyptPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptDepartment of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif, Saudi ArabiaPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptInstitut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université de Montpellier, ENSCM, Montpellier, FrancePharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, EgyptA novel series of 2-thioacetamide linked benzoxazole-benzamide conjugates 1–15 was designed as potential inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The prepared compounds were evaluated for their potential antitumor activity and their corresponding selective cytotoxicity was estimated using normal human fibroblast (WI-38) cells. Compounds 1, 9–12 and 15 showed good selectivity and displayed excellent cytotoxic activity against both HCT-116 and MCF-7 cancer cell lines compared to sorafenib, used as a reference compound. Furthermore, compounds 1 and 11 showed potent VEGFR-2 inhibitory activity. The cell cycle progression assay showed that 1 and 11 induced cell cycle arrest at G2/M phase, with a concomitant increase in the pre-G1 cell population. Further pharmacological studies showed that 1 and 11 induced apoptosis and inhibited the expression of the anti-apoptotic Bcl-2 and Bcl-xL proteins in both cell lines. Therefore, compounds 1 and 11 might serve as promising candidates for future anticancer therapy development.https://www.tandfonline.com/doi/10.1080/14756366.2022.2081844Benzoxazole-benzamideanti-cancerapoptosisVEGFR-2 inhibitorsBcl-2 |
| spellingShingle | Ibrahim H. Eissa Radwan El-Haggar Mohammed A. Dahab Marwa F. Ahmed Hazem A. Mahdy Reem I. Alsantali Alaa Elwan Nicolas Masurier Samar S. Fatahala Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers Journal of Enzyme Inhibition and Medicinal Chemistry Benzoxazole-benzamide anti-cancer apoptosis VEGFR-2 inhibitors Bcl-2 |
| title | Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers |
| title_full | Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers |
| title_fullStr | Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers |
| title_full_unstemmed | Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers |
| title_short | Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers |
| title_sort | design synthesis molecular modeling and biological evaluation of novel benzoxazole benzamide conjugates via a 2 thioacetamido linker as potential anti proliferative agents vegfr 2 inhibitors and apoptotic inducers |
| topic | Benzoxazole-benzamide anti-cancer apoptosis VEGFR-2 inhibitors Bcl-2 |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2081844 |
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