Design, synthesis, and docking study of new quinoline derivatives as antitumor agents.

Autor: Nasr EE; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt., Mostafa AS; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt., El-Sayed MAA; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt., Massoud MAM; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2019 Jul; Vol. 352 (7), pp. e1800355. Date of Electronic Publication: 2019 May 13.
DOI: 10.1002/ardp.201800355
Abstrakt: 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 50 ) against the majority of them, including SR, HL-60 (TB) strains (leukemia), and MDA-MB-435 strains (melanoma), with GI 50 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 IC 50 value of 0.278 µM compared with camptothecin as a reference drug (IC 50 0.224 µM). Docking studies were performed to investigate the recognition profile of compound 13 with the Topo 1 enzyme binding site.
(© 2019 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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