Quinoline-Based p300 Histone Acetyltransferase Inhibitors with Pro-apoptotic Activity in Human Leukemia U937 Cells
Quinoline-Based p300 Histone Acetyltransferase Inhibitors with Pro-apoptotic Activity in Human Leukemia U937 Cells
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DOI：
10.1002/cmdc.201300536
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发表时间：
2014-03-01
期刊：
影响因子：
3.4
通讯作者：
Mai, Antonello
中科院分区：
文献类型：
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作者：
Lenoci, Alessia;Tomassi, Stefano;Mai, Antonello
对2-甲基-3-乙氧羰基喹啉（1）进行化学操作，这是我们研究小组先前鉴定的一种组蛋白乙酰转移酶抑制剂，在亚毫摩尔/毫摩尔水平上具有活性，导致在C2-喹啉位置上具有高级烷基或在C6-喹啉位置上具有额外侧链的化合物。这些化合物显示出对p300蛋白赖氨酸乙酰转移酶活性的至少三倍改善的抑制效力;它们中的一些降低了U937细胞中的组蛋白H3和H4乙酰化水平，并在处理U937细胞后诱导高度的细胞凋亡（三种化合物比化合物1高>10倍）。
Chemical manipulations performed on 2-methyl-3-carbethoxyquinoline (1), a histone acetyltransferase inhibitor previously identified by our research group and active at the sub-millimolar/millimolar level, led to compounds bearing higher alkyl groups at the C2-quinoline or additional side chains at the C6-quinoline positions. Such compounds displayed at least threefold improved inhibitory potency toward p300 protein lysine acetyltransferase activity; some of them decreased histone H3 and H4 acetylation levels in U937 cells and induced high degrees of apoptosis (three compounds >10-fold higher than compound 1) after treatment of U937 cells.