Issue 1, 2018

Phenylethynyl-substituted heterocycles inhibit cyclin D1 and induce the expression of cyclin-dependent kinase inhibitor p21Wif1/Cip1 in colorectal cancer cells

Abstract

Fluorinated phenylethynyl-substituted heterocycles that possessed either an N-methylamino or N,N-dimethylamino group attached to heterocycles including pyridines, indoles, 1H-indazoles, quinolines, and isoquinolines inhibited the proliferation of LS174T colon cancer cells in which the inhibition of cyclin D1 and induction of the cyclin-dependent kinase inhibitor-1 (i.e., p21Wif1/Cip1) served as readouts for antineoplastic activity at a cellular level. At a molecular level, these agents, particularly 4-((2,6-difluorophenyl)ethynyl)-N-methylisoquinolin-1-amine and 4-((2,6-difluorophenyl)ethynyl)-N,N-dimethylisoquinolin-1-amine, bound and inhibited the catalytic subunit of methionine S-adenosyltransferase-2 (MAT2A).

Graphical abstract: Phenylethynyl-substituted heterocycles inhibit cyclin D1 and induce the expression of cyclin-dependent kinase inhibitor p21Wif1/Cip1 in colorectal cancer cells

Article information

Article type
Research Article
Submitted
31 Jul 2017
Accepted
30 Oct 2017
First published
03 Nov 2017

Med. Chem. Commun., 2018,9, 87-99

Phenylethynyl-substituted heterocycles inhibit cyclin D1 and induce the expression of cyclin-dependent kinase inhibitor p21Wif1/Cip1 in colorectal cancer cells

V. M. Sviripa, L. M. Kril, W. Zhang, Y. Xie, P. Wyrebek, L. Ponomareva, X. Liu, Y. Yuan, C. Zhan, D. S. Watt and C. Liu, Med. Chem. Commun., 2018, 9, 87 DOI: 10.1039/C7MD00393E

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