Design and Synthesis of (2-oxo-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents
| Autor: | El-Sheref, Essmat M., Elbastawesy, Mohammed A. I., Brown, Alan B., Shawky, Ahmed M., Gomaa, Hesham A. M., Bräse, Stefan, Youssif, Bahaa G. M. |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
anti-proliferative
Molecular Structure apoptosis Organic chemistry Antineoplastic Agents Cell Cycle Checkpoints Triazoles click azido Article Structure-Activity Relationship triazole QD241-441 Cell Line Tumor MCF-7 Cells Humans Click Chemistry quinolones Drug Screening Assays Antitumor Copper Cell Proliferation |
| Zdroj: | Molecules, Vol 26, Iss 6798, p 6798 (2021) Molecules Volume 26 Issue 22 |
| ISSN: | 1420-3049 |
| Popis: | A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)bis(4-hydroxyquinolin-2(1H)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products are interesting precursors for their anti-proliferative activity. Compound 8g was the most active one, achieving IC50 = 1.2 ± 0.2 µM and 1.4 ± 0.2 µM against MCF-7 and Panc-1 cell lines, respectively. Moreover, cell cycle analysis of cells MCF-7 treated with 8g showed cell cycle arrest at the G2/M phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant pro-apoptotic activity is indicated by annexin V-FITC staining. |
| Databáze: | OpenAIRE |
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