Open AccessPhenylethynyl-substituted heterocycles inhibit cyclin D1 and induce the expression of cyclin-dependent kinase inhibitor p21Wif1/Cip1in colorectal cancer cells
Author(s) -
Vitaliy M. Sviripa,
Liliia M. Kril,
Wen Zhang,
Yanqi Xie,
Przemysław Wyrębek,
Larissa V. Ponomareva,
Xifu Liu,
Yaxia Yuan,
Zhan Chen,
David S. Watt,
Chunming Liu
Publication year - 2018
Publication title -
medchemcomm
Language(s) - English
Resource type - Journals
eISSN - 2040-2511
pISSN - 2040-2503
DOI - 10.1039/c7md00393e
Subject(s) - cyclin d1 , kinase , chemistry , amine gas treating , cyclin d , colorectal cancer , protein subunit , cancer research , stereochemistry , biochemistry , cancer , cell cycle , biology , cell , gene , organic chemistry , genetics
Fluorinated, phenylethynyl-substituted heterocycles that possessed either an N -methylamino or N,N -dimethylamino group attached to heterocycles including pyridines, indoles, 1 H -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 ., p21 Wif1/Cip1 ) served as a readout for antineoplastic activity at a cellular level. On 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).