Design, Synthesis, Anti-Proliferative Evaluation and Cell Cycle Analysis of Hybrid 2-Quinolones
| Autor: | Heba Abd El Hady Mohamed, Hossa F. Al-Shareef |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
Cell cycle checkpoint Antineoplastic Agents Quinolones 010402 general chemistry 01 natural sciences chemistry.chemical_compound Structure-Activity Relationship medicine Cytotoxic T cell Humans Doxorubicin Propidium iodide IC50 Cell Proliferation Pharmacology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Cell Cycle Hep G2 Cells Small molecule Combinatorial chemistry 0104 chemical sciences chemistry Apoptosis Drug Design Molecular Medicine Drug Screening Assays Antitumor DNA medicine.drug |
| Zdroj: | Anti-cancer agents in medicinal chemistry. 19(9) |
| ISSN: | 1875-5992 |
| Popis: | Background: Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Methods: Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. Results: A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Conclusion: Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control. |
| Databáze: | OpenAIRE |
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