Pseudoceramines A-D, new antibacterial bromotyrosine alkaloids from themarine sponge Pseudoceratina sp.

Abstract

Bioassay-guided fractionation of the CH2Cl2/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 (IC50 = 19 and 6 mM, respectively) and the enzyme activity of YopH (IC50 = 33 and 6 mM, respectively).