Vitaliy M Sviripa1,2, Liliia M Kril2,3, Wen Zhang3,4, Yanqi Xie3,4, Przemyslaw Wyrebek2,3, Larissa Ponomareva1,2, Xifu Liu5, Yaxia Yuan1,2,6, Chang-Guo Zhan1,2,6, David S Watt1,2,5,3,4, Chunming Liu5,3,4. 1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596. 2. Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596. 3. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536-0509. 4. Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536-0093. 5. Epionc, Inc., P.O. Box 23436, Lexington, KY 40523. 6. Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky 40536-0596.
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 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).
Fluorinated, n class="Chemical">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 LS174Tcolon cancer cells in which the inhibition of cyclin D1 and induction of the cyclin-dependent kinase inhibitor-1 (i.e., p21Wif1/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).
Authors: Wen Zhang; Vitaliy Sviripa; Liliia M Kril; Xi Chen; Tianxin Yu; Jiandang Shi; Piotr Rychahou; B Mark Evers; David S Watt; Chunming Liu Journal: J Med Chem Date: 2011-02-03 Impact factor: 7.446
Authors: Vitaliy M Sviripa; Wen Zhang; Liliia M Kril; Alice X Liu; Yaxia Yuan; Chang-Guo Zhan; Chunming Liu; David S Watt Journal: Bioorg Med Chem Lett Date: 2014-05-09 Impact factor: 2.823
Authors: Garrett M Morris; Ruth Huey; William Lindstrom; Michel F Sanner; Richard K Belew; David S Goodsell; Arthur J Olson Journal: J Comput Chem Date: 2009-12 Impact factor: 3.376
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