来自面包树和香彩雀的刺猬抑制剂。
Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens.
作者信息
Arai Midori A, Uchida Kyoko, Sadhu Samir K, Ahmed Firoj, Koyano Takashi, Kowithayakorn Thaworn, Ishibashi Masami
机构信息
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
出版信息
Bioorg Med Chem. 2015 Aug 1;23(15):4150-4154. doi: 10.1016/j.bmc.2015.06.058. Epub 2015 Jul 2.
The hedgehog (Hh) signaling pathway plays crucial roles in cell maintenance and proliferation during embryonic development. Naturally occurring Hh inhibitors were isolated from Artocarpus communis and Hyptis suaveolens using our previously constructed cell-based assay system. Bioactivity guided fractionation led to the isolation of 15 compounds, including seven new compounds (4, 5, 6, 7, and 9-11). The isolated compounds showed cytotoxicity against a cancer cell line (PANC1) in which Hh signaling was abnormally activated. Several compounds (12-14; GLI1 transcriptional inhibition IC50=7.6, 4.7, and 4.0 μM, respectively) inhibited Hh related protein (BCL2) expression. Moreover, compounds 1, 12, and 13 disrupted GLI1 and DNA complex formation.
刺猬信号通路（Hh）在胚胎发育过程中的细胞维持和增殖中起着关键作用。利用我们之前构建的基于细胞的检测系统，从面包树和香苦草中分离出了天然存在的Hh抑制剂。生物活性导向的分级分离导致分离出15种化合物，包括7种新化合物（4、5、6、7和9 - 11）。分离出的化合物对Hh信号异常激活的癌细胞系（PANC1）显示出细胞毒性。几种化合物（12 - 14；GLI1转录抑制IC50分别为7.6、4.7和4.0 μM）抑制了Hh相关蛋白（BCL2）的表达。此外，化合物1、12和13破坏了GLI1与DNA复合物的形成。
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