Sponges psammaplin

There have been three reports of the same dimeric disulfide. It was first isolated from an unidentified sponge from Guam and the structure elucidated by analysis of spectral data. The (E,E) stereochemistry of the disulfide (500) was defined by comparing the I3C NMR spectroscopic data with those of the (E,Z)-isomer (501) that was obtained as an unstable minor product [425]. Compound 500 was isolated from a species of Psammaplysilla and was called psammaplin A [426]. It was also isolated from Thorectopsamma xana, collected from the same location in Guam, together with a minor dimeric metabolite bisaprasin (502). Both compounds inhibited growth of Staphylococcus aureus and Bacillus subtilis [427]. Psammaplin A (bisprasin) (500) was later isolated from a Dysidea species of sponge and shown to act on Ca2+-induced Ca2+ release channels of skeletal muscle [428]. 

Pham NB, Butler MS, Quinn RJ (2000) Isolation of Psammaplin A 11 -Sulfate and Bisaprasin 11 -Sulfate from the Marine Sponge Aplysinella rhax. J Nat Prod 63 393... 

Tabudravu JN, Eijsink VGH, Gooday GW, Jaspars M, Komander D, Legg M, Synstad B, van Aalten DMF (2002) Psammaplin A, a Chitinase Inhibitor Isolated from the Fijian Marine Sponge Aplysinella rhax. Bioorg Med Chem 10 1123... 

A second example of an activated chemical defense concerns the Indo Pacific sponge Aplysinella rhax, in which tissue damage results in the rapid enzymatic transformation of psammaplin A sulfate 63 into psammaplin A 64 exposure of 63 to tissue from other sponges does not result in any conversion. Compound 63 deters feeding by reef fish, but when offered a choice between psammaplin A and its sulfate, both foods were avoided. In aquarium assays with C. solandri, extracts of damaged tissue were more deterrent than extracts from intact tissue, but both treatments were less palatable than control foods. In choice experiments, C. solandri preferred food treated with 63 over 64.104... 

The isolation of psammaplin derivatives from the sponge PsammaplysiUa purpurea, in particular the only nonhalogenated analog, prepsammaplin A (105), allowed Jimenez and Crews to propose a biogenesis for this family of amino acid derivatives in which psammaplin A is formed by the linear combination of two bromotyrosine oxime derivatives and two rearranged cysteines [102]. 

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). 

Mora FD, Jones DK, Desai PV, et al. Bioassay for the identification of natural product-based activators of peroxisome proliferator-activated receptor-y (PPARy) the marine sponge metabolite psammaplin A activates PPARy and induces apoptosis in human breast cancer cells. J Nat Prod 2006 69 547-522. 

Psammaplin A is a symmetrical bromotyrosine-derived disulfide dimer isolated from a marine sponge Psammalysilla, which exhibits in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (Figure 11.96). ° In order to find potent and structurally simplified analogs of psammaplin A that could be used as tools for SAR smdies, Nicolaou et al. undertook the combinatorial synthesis of a library of disulfide-containing molecules using a pool of 88 synthetic... 

Jimenez, C. and Crews, P. (1991) Novel marine sponge-derived aminoacids 13. Additional psammaplin derivatives from Psammaplysilla purpurea. Tetrahedron, 47, 2097-2102. 

Kim, D Lee, I.S., Jung, J.H., and Yang, S.-l. (1999a) Psammaplin A, a natural bromotyrosine derivative from a sponge, possesses the antibacterial activity against methicillin-resistant Staphylococcus aureus and the DNA gyrase-inhibitory activity. Arch. Pharm. Res., 22, 25-29. 

Pham, N.B., Butler, M.S., and Quinn, R.J. (2000) Isolation of psammaplin A 112-sulfate and bisaprasin ll-suFate from the marine sponge Aplysinella rhax. J. Nat. Prod., 63, 393-395. 

Scheuer et al. later reported the psammaplin A (152) and the psammaplin A dimer, bisaprasin (154), from the Guam sponge Thorectopsamma xana (109). 

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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