Pseudoceratina psammaplins

F (1997) is a potent histone deacetylase inhibitor, and psammaplin G (1998) is a potent DNA methyltransferase inhibitor. A Southern Japanese version of Pseudoceratina purpurea has yielded pseudoceratins A (2002) and B (2003) (1834). 

The marine bryozoan Amathia convoluta produces convolutamine H (72) [61], and the Japanese gastropod Turbo marmorata has yielded the highly toxic (LD99 1-4 mg/ kg, mice) iodinated turbotoxins A (73) and B (74) [62[. The Palauan ascidian Botrylloides tyreum contains botryllamide G (75) [63], and several new psammaplins, for example psammaplin E (76), have been isolated from the sponge Pseudoceratina purpurea [64]. 

Crews has also formulated a biosynthetic pathway for the disulfide bromotyrosine psammaplins from the sponge Pseudoceratina purpurea [64,126]. The structurally unique ma edamines (80, 81) may be derived from a dehydro derivative of aplysa-mine-2 or purpuramine H via cyclization and dehydroxylation [69]. The numerous bromotyrosine alkaloids that contain an aminopropanol unit, such as nakirodin A (71), may be derived from a homoserine unit through decarboxylation [60]. The... 

Bromotyrosine-derived metabolites are often encountered in marine sponges of the families Aplysinidae and Pseudocer-atidae, in particular Pseudoceratina (= Psammaplysilla) purpurea. They show a variety of biological activities, which include antimicrobial, enzyme inhibitory, and antifouling activities. Psammaplysin A (47) is antimicrobial, cytotoxic, and antifouling, whereas psammaplin A (48) is an inhibitor of histone deacetylase (2). The marine sponge lanthella basta synthesizes at least 25 bastadins that are linear or cyclic peptides composed of four bromotyrosine residues [bastadin 5 (49)] and show antimicrobial, cytotoxic, and enzyme inhibitory activities as well as interaction with Ca + channels (21). 

Crews et al. proposed a biogenetic pathway, based on the isolation of prep-sammaplin A (155), to rationalize the formation of psammaplin A (152) and other bromotyrosine derivatives isolated from Pseudoceratina purea by his group (110, 112). A straightforward dimerization of a rearranged cysteine (Cys = HS-CH2-CH2-NHCOOMe) could generate prepsammaplin A (155). Condensation of the dimer... 

Recently, psammaplins were reported as potent histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors (see Table X) (772). Eleven psammaplins (see Table X), isolated from the sponge Pseudoceratina purpurea, were tested in the histone deacetylase (HDAC) enzyme assay at concentrations ranging from 16 nM to 10 pM, and the data obtained were compared to that of two standards, trichostatin A 300) and trapoxin A 301). There were three psammaplin derivatives whose IC50 values were in a... 

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