One-pot three-component synthesis of novel spirooxindoles with potential cytotoxic activity against triple-negative breast cancer MDA-MB-231 cells
| Autor: | Hany S. Ibrahim, Hatem A. Abdel-Aziz, Wagdy M. Eldehna, Hazem A. Ghabbour, Ahmed R. Hamed, Dina H. EL-Naggar |
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| Rok vydání: | 2017 |
| Předmět: |
Indoles
spirooxindoles EGFR Antineoplastic Agents Triple Negative Breast Neoplasms Malignancy 01 natural sciences Cell Line Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Breast cancer Triple-negative breast cancer Drug Discovery medicine Humans Cytotoxic T cell Spiro Compounds Cell Proliferation Mda mb 231 Pharmacology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry business.industry Cell Cycle lcsh:RM1-950 apoptosis Treatment options General Medicine medicine.disease humanities 0104 chemical sciences lcsh:Therapeutics. Pharmacology Apoptosis 030220 oncology & carcinogenesis Molecular targets Cancer research anti-proliferative activity Drug Screening Assays Antitumor business Research Paper |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 33, Iss 1, Pp 309-318 (2018) Journal of Enzyme Inhibition and Medicinal Chemistry |
| ISSN: | 1475-6374 1475-6366 |
| DOI: | 10.1080/14756366.2017.1417276 |
| Popis: | Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with limited treatment options due to its heterogeneity and the lack of well-defined molecular targets. In our endeavour towards the development of novel anti-TNBC agents, herein we report a one-pot three-component synthesis of novel spirooxindoles 6a–p, and evaluation of their potential anti-proliferative activity towards TNBC MDA-MB-231 cells. Spirooxindoles 6a, 6e and 6i emerged as the most potent analogues with IC50 = 6.70, 6.40 and 6.70 µM, respectively. Compounds 6a and 6e induced apoptosis in MDA-MB-231 cells, as evidenced by the up-regulation of the Bax and down-regulation of the Bcl-2, besides boosting caspase-3 levels. Additionally, 6e displayed significant increase in the percent of annexin V-FITC positive apoptotic cells from 1.34 to 44%. Furthermore, spirooxindoles 6e and 6i displayed good inhibitory activity against EGFR (IC50 = 120 and 150 nM, respectively). Collectively, these data demonstrated that 6e might be a potential lead compound for the development of effective anti-TNBC agents. |
| Databáze: | OpenAIRE |
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