Cryptocaryols A-H, α-pyrone-containing 1,3-polyols from Cryptocarya sp. implicated in stabilizing the tumor suppressor Pdcd4.
Cryptocaryols A-H, α-pyrone-containing 1,3-polyols from Cryptocarya sp. implicated in stabilizing the tumor suppressor Pdcd4.
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DOI：
10.1021/np100918z
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发表时间：
2011-05-27
影响因子：
5.1
通讯作者：
Gustafson KR
中科院分区：
文献类型：
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作者：
Grkovic T;Blees JS;Colburn NH;Schmid T;Thomas CL;Henrich CJ;McMahon JB;Gustafson KR
设计用于鉴定肿瘤抑制因子Pdcd 4的小分子稳定剂的高通量基于细胞的报告基因测定用于筛选NCI天然产物库中的提取物。从巴布亚新几内亚采集的热带树木Cryptocarya sp.的提取物中进行生物测定指导的分馏，提供了一系列新的含5，6-二氢-α-吡喃酮的1，3-多元醇（1-8），命名为cryptocaryols A-H。通过NMR、MS和CD研究结合NMR数据库比较对其结构进行了归属。发现化合物1-8以1.3至4.9 μM的EC 50浓度从TPA诱导的降解中拯救Pdcd 4。
A high-throughput cell-based reporter assay designed to identify small-molecule stabilizers of the tumor suppressor Pdcd4 was used to screen extracts in the NCI Natural Products Repository. Bioassay-guided fractionation of an extract from a Papua New Guinea collection of the tropical tree Cryptocarya sp. provided a series of new 5,6-dihydro-α-pyrone-containing 1,3-polyols (1–8), named cryptocaryols A–H. Their structures were assigned from a combination of NMR, MS, and CD studies in conjunction with NMR database comparisons. Compounds 1–8 were found to rescue Pdcd4 from TPA-induced degradation with EC50 concentrations that ranged from 1.3 to 4.9 µM.