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

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

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).

Concepts Keywords
Binding Site Enzyme inhibitor
Breast Docking
Camptothecin Chalcone
Cytotoxicity Lactones
Enzyme Lactams
Epithelial Camptothecin
Fibroblast Chalconoids
Leukemia Alkaloids
MB Medicinal chemistry
MDA Chemical compounds
Melanoma Chemistry
Moieties Organic compounds
Quinoline Strains melanoma
Quinolines TB
Topoisomerase
Weinheim

Semantics

Type Source Name
gene UNIPROT KDR
gene UNIPROT EGFR
drug DRUGBANK Camptothecin
gene UNIPROT RXFP2
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease DOID leukemia
disease MESH leukemia
disease MESH growth
disease DOID cancer
disease MESH cancer

Original Article

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