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Citation
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HERO ID
6343031
Reference Type
Journal Article
Title
Application of a catalyst-free Domino Mannich/Friedel-Crafts alkylation reaction for the synthesis of novel tetrahydroquinolines of potential antitumor activity
Author(s)
Castillo, JC; Jimenez, E; Portilla, J; Insuasty, B; Quiroga, J; Moreno-Fuquen, R; Kennedy, AR; Abonia, R
Year
2018
Is Peer Reviewed?
1
Journal
Tetrahedron
ISSN:
0040-4020
Volume
74
Issue
9
Page Numbers
932-947
Language
English
DOI
10.1016/j.tet.2017.12.049
Web of Science Id
WOS:000425559000003
URL
http:///www.elsevier.com
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Abstract
A useful and efficient method to construct diversely substituted 1,2,3,4-tetrahydroquinolines in good to excellent yields has been developed through a catalyst-free Domino Mannich and intramolecular Friedel-Crafts alkylation reactions of N-arylamines with paraformaldehyde and electron-rich olefins via the formation of N-aryl-N-alkylmethyleneiminium ions as the key intermediates to afford the target products. Nine of the new compounds were evaluated in the US National Cancer Institute (NCI), where compound 5f (R1 = 6-MeO, R2 = p-ClC6H4 and X = pyrrolidin-2-onyl) presented a remarkable activity against 57 cancer cell lines, with the most important GI50 values ranging from 1.46 to 8.28 M from in vitro assays. Further studies performed over the active compound 5f on HCT116 colon cancer cells indicated that its effect on cell death is exerted through a cell cycle arrest (S phase) in a dose dependent manner, as well as suppression on the cell proliferation process. (C) 2018 Elsevier Ltd. All rights reserved.
Keywords
Chemistry; Polymer Science; Tetrahydroquinolines, Multicomponent reaction, Mannich-type reaction,; Anticancer activity, Cell cycle arrest; convenient synthesis, derivatives, hydrogenation, inhibitors, series,
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