School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Eur J Med Chem. 2016 Oct 21;122:92-101. doi: 10.1016/j.ejmech.2016.06.023. Epub 2016 Jun 16.
This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N-hydroxyacrylamides (8a-k). Structure-activity relationship studies focusing on regio-effect of N-hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N-hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide (8f) showed remarkable enzymatic and cellular activity. The GI50 values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts.
本研究报告了 2-(苯磺酰基)喹啉 N-羟基丙烯酰胺（8a-k）的设计和合成。重点研究了 N-羟基丙烯酰胺部分的区域效应和磺酰基连接基的影响的构效关系研究表明，N-羟基-3-[3-（喹啉-2-磺酰基）-苯基]-丙烯酰胺（8f）表现出显著的酶和细胞活性。化合物 8f 对 HL-60、HCT116、PC-3 和 A549 细胞的 GI50 值分别为 0.29、0.08、0.15 和 0.27 μM。因此，它们比 FDA 批准的 PXD-101 和 SAHA 更有效。它们还对组蛋白 H3 和微管蛋白α的乙酰化程度有影响。在体内研究中，8f 明显抑制了 HCT116 异种移植物的生长。
