Design, Synthesis, Anti-Proliferative Evaluation and Cell Cycle Analysis of Hybrid 2-Quinolones

Abstract

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.

Synthesis and biological evaluation of hybrid quinolone-based quaternary ammonium antibacterial agents

“…These results may indicate strong correlation between antibacterial activity and lipophilic properties of the tested antibacterial agents. This observation stays in agreement with a general principle that antibacterial and antiproliferative activities of fluoroquinolones strongly depends on lipophilic profile, which condition their diffusion into bacterial [42,43] and human cancer cells [44,45]. In this context, increase in the overall lipophilic character of a quinolone derivative usually involves introduction of a bulky group at the N-4 position of piperazine, or more generally, at the C-7 position of the parent drug [42].…”

Synthesis and antitumor potential of new arylidene ursolic acid derivatives via caspase‐8 activation

“…The synthesis, the physical properties, and the biological activities of hybrid compounds containing different heterocyclic fragments have been widely investigated. [30][31][32][33] Motivated by these findings, we designed and synthesized new arylidene UA derivatives incorporating oxygen-, sulfur-, and nitrogen-containing heterocycles. Furan, thiophene, pyridine, and pyrimidine derivatives were reported to have antitumor activity.…”

Synthesis of some novel 2-(3-cyano -6-(thiophen- 2-yl)-4,4′- bipyridin-2- yloxy)acetohydrazide derivatives: assessment of their cytotoxic activity

“…Compounds containing a pyridine group that includes a cyano group have excellent antitumor activity as reported in the previous publications [9 -15]. Based on the reported biological activity of these heterocyclic moieties [16,17], Schiff bases [18][19][20], triazoles [21,22], quinolones and spiro compounds [23,24] as anticancer agents [25] and continuing of my research on the chemistry of the biologically active compounds [25][26][27][28][29][30]. Herein, I designed new biologically active compounds using 2-(6′-(4-chlorophenyl) -3′-cyano-3,4′bipyridin-2′-yloxy) acetohydrazide(3) as a building block and studying their antitumor activity against breast cancer cell line.…”