Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2Inhibitors
In this work, design, synthesis, and screening of thiophene carboxamides 4–13 and 16–23 as dual vascular endothelial growth factor receptors (VEGFRs) and mitotic inhibitors was reported. All compounds were screened against two gastrointestinal solid cancer cells, HepG-2 and HCT-116 cell lines. The m...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2018.1503654 |
| _version_ | 1818144982492512256 |
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| author | Mohammed K. AbdElhameid Madlen B. Labib Ahmed T. Negmeldin Muhammad Al-Shorbagy Manal R. Mohammed |
| author_facet | Mohammed K. AbdElhameid Madlen B. Labib Ahmed T. Negmeldin Muhammad Al-Shorbagy Manal R. Mohammed |
| author_sort | Mohammed K. AbdElhameid |
| collection | DOAJ |
| description | In this work, design, synthesis, and screening of thiophene carboxamides 4–13 and 16–23 as dual vascular endothelial growth factor receptors (VEGFRs) and mitotic inhibitors was reported. All compounds were screened against two gastrointestinal solid cancer cells, HepG-2 and HCT-116 cell lines. The most active cytotoxic derivatives 5 and 21 displayed 2.3- and 1.7-fold higher cytotoxicity than Sorafenib against HepG-2 cells. Cell cycle and apoptosis analyses for compounds 5 and 21 showed cells accumulation in the sub-G1 phase, and cell cycle arrest at G2/M phase. The apoptotic inducing activities of compounds 5 and 21were correlated to the elevation of p53, increase in Bax/Bcl-2 ratio, and increase in caspase-3/7.Compounds 5 and 21 showed potent inhibition againstVEGFR-2 (IC50 = 0.59 and 1.29 μM) and β-tubulin polymerization (73% and 86% inhibition at their IC50 values).Molecular docking was performed with VEGFR-2 and tubulin binding sites to explain the displayed inhibitory activities. |
| first_indexed | 2024-12-11T11:56:13Z |
| format | Article |
| id | doaj.art-405d71918f00495f8af8f66f0ed1fcf8 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-11T11:56:13Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-405d71918f00495f8af8f66f0ed1fcf82022-12-22T01:08:11ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742018-01-013311472149310.1080/14756366.2018.15036541503654Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2InhibitorsMohammed K. AbdElhameid0Madlen B. Labib1Ahmed T. Negmeldin2Muhammad Al-Shorbagy3Manal R. Mohammed4Cairo UniversityBeni-Suef UniversityCairo UniversityCairo UniversityNational Center for Radiation Research and TechnologyIn this work, design, synthesis, and screening of thiophene carboxamides 4–13 and 16–23 as dual vascular endothelial growth factor receptors (VEGFRs) and mitotic inhibitors was reported. All compounds were screened against two gastrointestinal solid cancer cells, HepG-2 and HCT-116 cell lines. The most active cytotoxic derivatives 5 and 21 displayed 2.3- and 1.7-fold higher cytotoxicity than Sorafenib against HepG-2 cells. Cell cycle and apoptosis analyses for compounds 5 and 21 showed cells accumulation in the sub-G1 phase, and cell cycle arrest at G2/M phase. The apoptotic inducing activities of compounds 5 and 21were correlated to the elevation of p53, increase in Bax/Bcl-2 ratio, and increase in caspase-3/7.Compounds 5 and 21 showed potent inhibition againstVEGFR-2 (IC50 = 0.59 and 1.29 μM) and β-tubulin polymerization (73% and 86% inhibition at their IC50 values).Molecular docking was performed with VEGFR-2 and tubulin binding sites to explain the displayed inhibitory activities.http://dx.doi.org/10.1080/14756366.2018.1503654Gastrointestinal carcinomaHepG-2HCT-116thiophene carboxamideβ-tubulinangiogenesis |
| spellingShingle | Mohammed K. AbdElhameid Madlen B. Labib Ahmed T. Negmeldin Muhammad Al-Shorbagy Manal R. Mohammed Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2Inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry Gastrointestinal carcinoma HepG-2 HCT-116 thiophene carboxamide β-tubulin angiogenesis |
| title | Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2Inhibitors |
| title_full | Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2Inhibitors |
| title_fullStr | Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2Inhibitors |
| title_full_unstemmed | Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2Inhibitors |
| title_short | Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives on hepatocellular carcinomaas VEGFR-2Inhibitors |
| title_sort | design synthesis and screening of ortho amino thiophene carboxamide derivatives on hepatocellular carcinomaas vegfr 2inhibitors |
| topic | Gastrointestinal carcinoma HepG-2 HCT-116 thiophene carboxamide β-tubulin angiogenesis |
| url | http://dx.doi.org/10.1080/14756366.2018.1503654 |
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