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).

中文翻译：

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苯^乙炔基取代的杂环抑制大肠癌细胞中的细胞周期蛋白D1并诱导细胞周期蛋白依赖性激酶抑制剂p21 ^{Wif1 / Cip1的}表达

氟苯基乙炔基取代的杂环具有N-甲基氨基或与N，N-二甲基氨基连接的杂环，包括吡啶，吲哚，1 H-吲唑，喹啉和异喹啉，可抑制LS174T结肠癌细胞的增殖，其中Cyclin的抑制作用D1和细胞周期蛋白依赖性激酶抑制剂-1（即p21 ^{Wif1 / Cip1}）的^诱导用作细胞水平抗肿瘤活性的读数。在分子水平上，这些试剂，特别是4-（（2,6-二氟苯基）乙炔基）-N-甲基异喹啉-1-胺和4-（（2,6-二氟苯基）乙炔基）-N，N-二甲基异喹啉-1-胺结合并抑制蛋氨酸S-腺苷基转移酶2（MAT2A）的催化亚基。