Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia.
Org Biomol Chem. 2011 Oct 7;9(19):6755-60. doi: 10.1039/c1ob05581j. Epub 2011 Aug 17.
Bioassay-guided fractionation of the CH(2)Cl(2)/MeOH extract of the Australian marine sponge Pseudoceratina sp. resulted in the purification of four new bromotyrosine alkaloids, pseudoceramines A-D (1-4), along with a known natural product, spermatinamine (5). The structures of 1-5 were determined by spectroscopic methods. Pseudoceramines A (1) and B (2) feature a rare bromotyrosyl-spermine-bromotyrosyl sequence, and pseudoceramine C (3) is the first example of bromotyrosine coupled with an N-methyl derivative of spermidine. Compounds 1-5 were screened for inhibition of toxin secretion by the type III secretion (T3S) pathway in Yersinia pseudotuberculosis. Compounds 2 and 5 inhibited secretion of the Yersinia outer protein YopE (IC(50) = 19 and 6 μM, respectively) and the enzyme activity of YopH (IC(50) = 33 and 6 μM, respectively).
基于生物活性的导向分离，从澳大利亚海绵 Pseudoceratina sp 的 CH(2)Cl(2)/MeOH 提取物中分离得到了四个新的溴代酪氨酸生物碱，分别为 pseudoceramines A-D（1-4），以及一个已知的天然产物，精胺（5）。通过光谱方法确定了 1-5 的结构。pseudoceramines A（1）和 B（2）具有罕见的溴代酪氨酸-精胺-溴代酪氨酸序列，而 pseudoceramine C（3）是首例溴代酪氨酸与亚精胺的 N-甲基衍生物相连的化合物。对 1-5 进行了抑制耶尔森氏菌 III 型分泌（T3S）途径分泌毒素的筛选。化合物 2 和 5 抑制了耶尔森氏菌外蛋白 YopE 的分泌（IC(50) = 19 和 6 μM）和 YopH 的酶活性（IC(50) = 33 和 6 μM）。
