Stadler Marc, Bitzer Jens, Mayer-Bartschmid Anke, Müller Hartwig, Benet-Buchholz Jordi, Gantner Florian, Tichy Hans-Volker, Reinemer Peter, Bacon Kevin B
InterMed Discovery GmbH (IMD), Otto-Hahn-Strasse 15, D-44227 Dortmund, Germany.
J Nat Prod. 2007 Feb;70(2):246-52. doi: 10.1021/np060162u. Epub 2007 Jan 24.
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).
从一株陆地链霉菌中分离得到了肉桂酰胺A - G（1 - 7），它们是人类20S蛋白酶体的强效和选择性抑制剂。它们的化学和生物学性质与盐孢酰胺A相似，盐孢酰胺A是最近从一种专性海洋放线菌中鉴定出的先导化合物，目前正作为一种抗癌药物进行开发。肉桂酰胺F和G（6, 7）结合了盐孢酰胺A和乳胞素的关键结构特征，在体外显示出大致相同的效力，IC50值在1 nM范围内。报道了产生菌的性质和系统发育位置、化合物1 - 7的生产和分离、通过质谱和核磁共振对其结构的阐明以及它们的生物活性。此外，还获得了肉桂酰胺A（1）的X射线晶体结构。
