Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer
In this work, the natural piperine moiety was utilised to develop two sets of piperine-based amides (5a–i) and ureas (8a–y) as potential anticancer agents. The anticancer action was assessed against triple negative breast cancer (TNBC) MDA-MB-231, ovarian A2780CP and hepatocellular HepG2 cancer cell...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2021.1988944 |
| _version_ | 1819177268716503040 |
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| author | Diaaeldin M. Elimam Abdullah A. Elgazar Fardous F. El-Senduny Ramadan A. El-Domany Farid A Badria Wagdy M. Eldehna |
| author_facet | Diaaeldin M. Elimam Abdullah A. Elgazar Fardous F. El-Senduny Ramadan A. El-Domany Farid A Badria Wagdy M. Eldehna |
| author_sort | Diaaeldin M. Elimam |
| collection | DOAJ |
| description | In this work, the natural piperine moiety was utilised to develop two sets of piperine-based amides (5a–i) and ureas (8a–y) as potential anticancer agents. The anticancer action was assessed against triple negative breast cancer (TNBC) MDA-MB-231, ovarian A2780CP and hepatocellular HepG2 cancer cell lines. In particular, 8q stood out as the most potent anti-proliferative analogue against TNBC MDA-MB-231 cells with IC50 equals 18.7 µM, which is better than that of piperine (IC50 = 47.8 µM) and 5-FU (IC50 = 38.5 µM). Furthermore, 8q was investigated for its possible mechanism of action in MDA-MB-231 cells via Annexin V-FITC apoptosis assay and cell cycle analysis. Moreover, an in-silico analysis has proposed VEGFR-2 as a probable enzymatic target for piperine-based derivatives, and then has explored the binding interactions within VEGFR-2 active site (PDB:4ASD). Finally, an in vitro VEGFR-2 inhibition assay was performed to validate the in silico findings, where 8q showed good VEGFR-2 inhibitory activity with IC50 = 231 nM. |
| first_indexed | 2024-12-22T21:23:58Z |
| format | Article |
| id | doaj.art-954f778825b3476294581618b513a4fa |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-22T21:23:58Z |
| publishDate | 2022-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-954f778825b3476294581618b513a4fa2022-12-21T18:12:07ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-01-01371395010.1080/14756366.2021.19889441988944Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancerDiaaeldin M. Elimam0Abdullah A. Elgazar1Fardous F. El-Senduny2Ramadan A. El-Domany3Farid A Badria4Wagdy M. Eldehna5Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh UniversityDepartment of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh UniversityDepartment of Biochemistry, Faculty of Science, Mansoura UniversityDepartment of Microbiology and Immunology, Faculty of Pharmacy, Kafrelsheikh UniversityDepartment of Pharmacognosy, Faculty of Pharmacy, Mansoura UniversityDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh UniversityIn this work, the natural piperine moiety was utilised to develop two sets of piperine-based amides (5a–i) and ureas (8a–y) as potential anticancer agents. The anticancer action was assessed against triple negative breast cancer (TNBC) MDA-MB-231, ovarian A2780CP and hepatocellular HepG2 cancer cell lines. In particular, 8q stood out as the most potent anti-proliferative analogue against TNBC MDA-MB-231 cells with IC50 equals 18.7 µM, which is better than that of piperine (IC50 = 47.8 µM) and 5-FU (IC50 = 38.5 µM). Furthermore, 8q was investigated for its possible mechanism of action in MDA-MB-231 cells via Annexin V-FITC apoptosis assay and cell cycle analysis. Moreover, an in-silico analysis has proposed VEGFR-2 as a probable enzymatic target for piperine-based derivatives, and then has explored the binding interactions within VEGFR-2 active site (PDB:4ASD). Finally, an in vitro VEGFR-2 inhibition assay was performed to validate the in silico findings, where 8q showed good VEGFR-2 inhibitory activity with IC50 = 231 nM.http://dx.doi.org/10.1080/14756366.2021.1988944anticancerpiperic acidvegfr-2 inhibitorsmolecular dockingtriple negative breast cancernatural products |
| spellingShingle | Diaaeldin M. Elimam Abdullah A. Elgazar Fardous F. El-Senduny Ramadan A. El-Domany Farid A Badria Wagdy M. Eldehna Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer Journal of Enzyme Inhibition and Medicinal Chemistry anticancer piperic acid vegfr-2 inhibitors molecular docking triple negative breast cancer natural products |
| title | Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer |
| title_full | Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer |
| title_fullStr | Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer |
| title_full_unstemmed | Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer |
| title_short | Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer |
| title_sort | natural inspired piperine based ureas and amides as novel antitumor agents towards breast cancer |
| topic | anticancer piperic acid vegfr-2 inhibitors molecular docking triple negative breast cancer natural products |
| url | http://dx.doi.org/10.1080/14756366.2021.1988944 |
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