Design, synthesis, and docking study of new quinoline derivatives as antitumor agents.
Eman E NasrAmany S MostafaMagda A A El-SayedMohammed A M MassoudPublished in: Archiv der Pharmazie (2019)
New quinolines substituted with various heterocycles and chalcone moieties were synthesized and evaluated as antitumor agents. All the synthesized compounds were in vitro screened against 60 human cancer cell lines. Compound 13 showed the highest cytotoxicity toward 58 cell lines, exhibiting distinct growth inhibition values (GI50 ) against the majority of them, including SR, HL-60 (TB) strains (leukemia), and MDA-MB-435 strains (melanoma), with GI50 values of 0.232, 0.260, and 0.300 µM, respectively. It exhibited great selectivity toward cancer cell lines, with less toxic effect against normal cells represented by skin fibroblast (BJ) and breast epithelial cell lines (MCF-10F). The enzyme inhibitory activity of compound 13 was evaluated against topoisomerase 1 (Topo 1), epidermal growth factor receptor and vascular endothelial growth factor receptor 2, where it displayed worthy Topo 1 inhibition activity with an IC50 value of 0.278 µM compared with camptothecin as a reference drug (IC50 0.224 µM). Docking studies were performed to investigate the recognition profile of compound 13 with the Topo 1 enzyme binding site.
Keyphrases
- epidermal growth factor receptor
- vascular endothelial growth factor
- papillary thyroid
- endothelial cells
- molecular dynamics
- escherichia coli
- squamous cell
- molecular dynamics simulations
- tyrosine kinase
- breast cancer cells
- molecular docking
- cell cycle arrest
- induced apoptosis
- protein protein
- advanced non small cell lung cancer
- mycobacterium tuberculosis
- bone marrow
- signaling pathway
- cell death
- wound healing
- small molecule
- induced pluripotent stem cells
- case control
- childhood cancer