Publication date: May 13, 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 (GI ) against the majority of them, including SR, HL-60 (TB) strains (leukemia), and MDA-MB-435 strains (melanoma), with GI values of 0.232, 0.260, and 0.300 uM, 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 IC value of 0.278 uM compared with camptothecin as a reference drug (IC 0.224 uM). Docking studies were performed to investigate the recognition profile of compound 13 with the Topo 1 enzyme binding site.
Nasr, E.E., Mostafa, A.S., El-Sayed, M.A.A., and Massoud, M.A.M. Design, synthesis, and docking study of new quinoline derivatives as antitumor agents. 22599. 2019 Arch Pharm (Weinheim).