Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity
| Autor: | Eavan McLoughlin, Abdelsattar M. Omar, Tarek S. Ibrahim, Mohamed M Hawwas, Azizah M. Malebari, Niamh M. O’Boyle, Zakaria K. Abdel-Samii, Ehab S. Taher, Yaseen A.M.M. Elshaier |
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| Rok vydání: | 2020 |
| Předmět: |
Cell cycle checkpoint
Stereochemistry lcsh:Medicine lcsh:RS1-441 Pharmaceutical Science Oxadiazole 01 natural sciences Article lcsh:Pharmacy and materia medica chemistry.chemical_compound hydrazone quinoline Drug Discovery combretastatin A-4 Cytotoxicity Combretastatin Combretastatin A-4 biology 010405 organic chemistry lcsh:R Quinoline apoptosis 0104 chemical sciences 010404 medicinal & biomolecular chemistry Tubulin chemistry tubulin Cancer cell biology.protein Molecular Medicine oxadiazole |
| Zdroj: | Pharmaceuticals Volume 13 Issue 11 Pharmaceuticals, Vol 13, Iss 393, p 393 (2020) |
| ISSN: | 1424-8247 |
| Popis: | A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound, 19h, demonstrated superior IC50 values ranging from 0.02 to 0.04 µ M against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting 19h&rsquo s selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, 19h caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that 19h holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin. |
| Databáze: | OpenAIRE |
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