Cinnabaramides A-G:: Analogues of lactacystin and salinosporamide from a terrestrial streptomycete
Cinnabaramides A-G:: Analogues of lactacystin and salinosporamide from a terrestrial streptomycete
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DOI：
10.1021/np060162u
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发表时间：
2007-02-01
影响因子：
5.1
通讯作者：
Bacon, Kevin B.
中科院分区：
文献类型：
--
作者：
Stadler, Marc;Bitzer, Jens;Bacon, Kevin B.
朱砂胺A-G(1-7)是从一株链霉菌中分离得到的，是人20S蛋白酶体的有效和选择性抑制剂。它们的化学和生物学特性类似于盐孢酰胺A，这是一种最近从一种专性海洋放线菌中发现的先导化合物，目前正在开发用于抗癌的药物。桂皮酰胺类化合物F和G(6，7)结合了盐孢酰胺A和lactacystin的基本结构特征，在体外表现出大致相同的效力，IC50值在1 NM范围内。报道了产生菌的性质和系统发育地位，化合物1-7的产生和分离，其结构经MS和核磁共振确证，以及它们的生物活性。此外，还从朱砂酰胺A(1)中获得了X-射线晶体结构。
The cinnabaramides A-G (1-7) were isolated from a terrestrial strain of Streptomyces as potent and selective inhibitors of the human 20S proteasome. Their chemical and biological properties resemble those of salinosporamide A, a recently identified lead compound from an obligate marine actinomycete, which is currently under development as an anticancer agent. Cinnabaramides F and G (6, 7) combine essential structural features of salinosporamide A and lactacystin and show about equal potency in vitro, with IC50 values in the 1 nM range. The properties and phylogenetic position of the producer organism, the production and isolation of compounds 1-7, their structure elucidation by MS and NMR, and their biological activities are reported. Additionally, an X-ray crystal structure was obtained from cinnabaramide A (1).