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

Vitaliy M. Sviripa; Liliia M. Kril; Wen Zhang; Yanqi Xie; Przemyslaw Wyrebek; Larissa Ponomareva; Xifu Liu; Yaxia Yuan; Chang Guo Zhan; David S. Watt; Chunming Liu

doi:10.1039/c7md00393e

Phenylethynyl-substituted heterocycles inhibit cyclin D1 and induce the expression of cyclin-dependent kinase inhibitor p21^Wif1/Cip1 in colorectal cancer cells

Vitaliy M. Sviripa, Liliia M. Kril, Wen Zhang, Yanqi Xie, Przemyslaw Wyrebek, Larissa Ponomareva, Xifu Liu, Yaxia Yuan, Chang Guo Zhan, David S. Watt, Chunming Liu

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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., p21^Wif1/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).

Original language	English (US)
Pages (from-to)	87-99
Number of pages	13
Journal	MedChemComm
Volume	9
Issue number	1
DOIs	https://doi.org/10.1039/c7md00393e
State	Published - 2018
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Organic Chemistry

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title = "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).",

author = "Sviripa, {Vitaliy M.} and Kril, {Liliia M.} and Wen Zhang and Yanqi Xie and Przemyslaw Wyrebek and Larissa Ponomareva and Xifu Liu and Yaxia Yuan and Zhan, {Chang Guo} and Watt, {David S.} and Chunming Liu",

note = "Publisher Copyright: {\textcopyright} 2018 The Royal Society of Chemistry.",

year = "2018",

doi = "10.1039/c7md00393e",

language = "English (US)",

volume = "9",

pages = "87--99",

journal = "MedChemComm",

issn = "2040-2503",

publisher = "Royal Society of Chemistry",

number = "1",

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T1 - Phenylethynyl-substituted heterocycles inhibit cyclin D1 and induce the expression of cyclin-dependent kinase inhibitor p21Wif1/Cip1 in colorectal cancer cells

AU - Sviripa, Vitaliy M.

AU - Kril, Liliia M.

AU - Zhang, Wen

AU - Xie, Yanqi

AU - Wyrebek, Przemyslaw

AU - Ponomareva, Larissa

AU - Liu, Xifu

AU - Yuan, Yaxia

AU - Zhan, Chang Guo

AU - Watt, David S.

AU - Liu, Chunming

PY - 2018

Y1 - 2018

N2 - 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).

AB - 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).

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DO - 10.1039/c7md00393e

M3 - Article

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SN - 2040-2503

VL - 9

SP - 87

EP - 99

JO - MedChemComm

JF - MedChemComm

IS - 1

ER -

Phenylethynyl-substituted heterocycles inhibit cyclin D1 and induce the expression of cyclin-dependent kinase inhibitor p21^Wif1/Cip1 in colorectal cancer cells

Abstract

ASJC Scopus subject areas

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