Design, synthesis, and cytotoxicity screening of new synthesized imidazolidine-2-thiones as VEGFR-2 enzyme inhibitors.
Islam ZakiHeba M M RamadanEl-Sherbiny H El-SayedMohamed Abd El-MoneimPublished in: Archiv der Pharmazie (2020)
A series of imidazolin-2-thione derivatives was synthesized and structurally confirmed through the use of different spectroscopic techniques such as infrared, nuclear magnetic resonance, and mass spectrometry along with elemental analyses. The breast cancer cell line MCF-7 was utilized in the evaluation of the cytotoxic activity of the prepared molecules. The tested molecules 3 and 7 exhibited the best results on MCF-7 cells, with mean IC50 values of 3.26 and 4.31 µM, respectively. The results of the VEGFR-2 assay indicated that compounds 3 and 7 displayed a good inhibition of the VEGFR-2 kinase enzyme. Additionally, DNA flow cytometry of compounds 3 and 7 showed cell cycle arrest at the G0/G1 phase, cell apoptosis, and marked DNA fragmentation in MCF-7 cells. Finally, compounds 3 and 7 were proved to upregulate the activation of effector caspase-3/7, as presented by the caspase-3/7 green flow cytometry assay.
Keyphrases
- cell cycle arrest
- flow cytometry
- cell death
- induced apoptosis
- pi k akt
- magnetic resonance
- breast cancer cells
- mass spectrometry
- endoplasmic reticulum stress
- signaling pathway
- vascular endothelial growth factor
- oxidative stress
- circulating tumor
- high throughput
- single molecule
- cell free
- high resolution
- computed tomography
- dendritic cells
- magnetic resonance imaging
- molecular docking
- contrast enhanced
- endothelial cells
- high performance liquid chromatography
- oxide nanoparticles