Design and synthesis of new trimethoxylphenyl-linked combretastatin analogues loaded on diamond nanoparticles as a panel for ameliorated solubility and antiproliferative activity
| Autor: | Islam Zaki, Amal M. Y. Moustafa, Botros Y. Beshay, Reham E. Masoud, Mohammed A. I. Elbastawesy, Mohammed A. S. Abourehab, Mohamed Y. Zakaria |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 37, Iss 1, Pp 2679-2701 (2022) |
| Druh dokumentu: | article |
| ISSN: | 14756366 1475-6374 1475-6366 |
| DOI: | 10.1080/14756366.2022.2116016 |
| Popis: | A new series of vinyl amide-, imidazolone-, and triazinone-linked combretastatin A-4 analogues have been designed and synthesised. These compounds have been evaluated for their cytotoxic activity against MDA-MB-231 breast cancer cells. The triazinone-linked combretastatin analogues (6 and 12) exhibited the most potent cytotoxic activity, in sub-micromolar concentration compared with combretastatin A-4 as a reference standard. The results of β-tubulin polymerisation inhibition assay appear to correlate well with the ability to inhibit β-tubulin polymerisation. Additionally, these compounds were subjected to biological assays relating to cell cycle aspects and apoptosis induction. In addition, the most potent compound 6 was loaded on PEG-PCL modified diamond nanoparticles (PEG-PCL-NDs) and F4 was picked as the optimum formula. F4 exhibited enhanced solubility and release over the drug suspension. In the comparative cytotoxic activity, PEG-PCL modified F4 was capable of diminishing the IC50 by around 2.89 times for nude F4, while by 3.48 times relative to non-formulated compound 6. |
| Databáze: | Directory of Open Access Journals |
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