Design, Synthesis and Anticancer Evaluation of Substituted Cinnamic Acid Bearing 2-Quinolone Hybrid Derivatives.
Ali Hussein Abu AlmaatyNermeen A ElgrahyEman FayadOla A Abu AliAhmed R E MahdyLamiaa A A BarakatMohammed El BeheryPublished in: Molecules (Basel, Switzerland) (2021)
A new series of hybrid molecules containing cinnamic acid and 2-quinolinone derivatives were designed and synthesized. Their structures were confirmed by 1H-NMR, 13C-NMR and mass analyses. All the synthesized hybrid molecules were assessed for their in vitro antiproliferative activity against more than one cancer cell lines. Compound 3-(3,5-dibromo-7,8-dihydroxy-4-methyl-2-oxoquinolin-1(2H)-ylamino)-3-phenylacrylic acid (5a) with IC50 = 1.89 μM against HCT-116 was proved to the most potent compound in this study, as compared to standard drug staurosporin. DNA flow cytometry assay of compound 5a revealed G2/M phase arrest and pre-G1 apoptosis. Annexin V-FITC showed that the percentage of early and late apoptosis was increased. The results of topoisomerase enzyme inhibition activity showed that the hybrid molecule 5a displays potent inhibitory activity compared with control.
Keyphrases
- flow cytometry
- cell cycle arrest
- high resolution
- magnetic resonance
- oxidative stress
- endoplasmic reticulum stress
- cell death
- solid state
- papillary thyroid
- squamous cell carcinoma
- single cell
- emergency department
- molecular docking
- young adults
- circulating tumor
- cell free
- signaling pathway
- squamous cell
- molecular dynamics simulations
- drug induced