Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens

被引：12
作者：
Arai, Midori A. [1 ]
Uchida, Kyoko [1 ]
Sadhu, Samir K. [2 ]
Ahmed, Firoj [3 ]
Koyano, Takashi [4 ]
Kowithayakorn, Thaworn [5 ]
Ishibashi, Masami [1 ]
机构：
[1] Chiba Univ, Grad Sch Pharmaceut Sci, Chuo Ku, Chiba 2608675, Japan
[2] Khulna Univ, Sch Life Sci, Pharm Discipline, Khulna 9208, Bangladesh
[3] Univ Dhaka, Dept Pharmaceut Chem, Dhaka 1000, Bangladesh
[4] Temko Corp, Nakano, Tokyo 1640012, Japan
[5] Khon Kaen Univ, Fac Agr, Khon Kaen 40002, Thailand
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 15期
基金：
日本学术振兴会;
关键词：
Natural products; Inhibitor; Hedgehog signal; Artocarpus communis; Hyptis suaveolens; MEDIATED TRANSCRIPTIONAL INHIBITORS; SMALL-MOLECULE INHIBITORS; SIGNALING PATHWAY; FLAVONOIDS; LEAVES; DITERPENOIDS; CYCLOPAMINE; BLOCKS;
D O I：
10.1016/j.bmc.2015.06.058
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 mu M, respectively) inhibited Hh related protein (BCL2) expression. Moreover, compounds 1, 12, and 13 disrupted GLI1 and DNA complex formation. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4150 / 4154
页数：5
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