Psammaplins from the Sponge Pseudoceratina purpurea: Inhibition of Both Histone Deacetylase and DNA Methyltransferase

Abstract

Four novel bisulfide bromotyrosine derivatives, psammaplins E (9), F (10), G (11), and H (12), and two new bromotyrosine derivatives, psammaplins I (13) and J (14), were isolated from the sponge Pseudoceratina purpurea, along with known psammaplins A (4), B (6), C (7), and D (8) and bisaprasin (5). The structures of psammaplins E (9) and F (10), which each contain an oxalyl group rarely found in marine organisms, were determined by spectroscopic analysis. Compounds 4, 5, and 10 are potent histone deacetylase inhibitors and also show mild cytotoxicity. Furthermore, compounds 4, 5, and 11 are potent DNA methyltransferase inhibitors. The biogenetic pathway previously proposed for the psammaplins class is also revisited.

The Marine Bromotyrosine Derivatives

“…Additional disulfide bromotyrosine derivatives, psammaplin E (159), F (160), G (161), H (162), I (163), and J (164) were isolated from the sponge Psammaplysilla purpurea collected from Papua New Guinea by Crews' group in 2003 (112). Psammaplin D (158) and H (162) possess a methyl or ethyl carbamate moiety, respectively.…”

“…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-CH 2 -CH 2 -NHCOOMe) could generate prepsammaplin A (155).…”

“…The amino group of the terminal α-amino acid (in 105, 106, and 93) or the dipeptide moiety (in 93) seems to be important for the activity, because the activity decreased in the order, (105). Araplysillins-I (99) and -II (100) inhibited the purified porcine brain Na,K-ATPase with IC 50 values of 0.5 mM and 1 mM, respectively, which is more significant than the parent alkaloids purealin (122) and lipopurealins (142) Recently, psammaplins were reported as potent histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors (see Table X) (112). 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 μM, and the data obtained were compared to that of two standards, trichostatin A (300) and trapoxin A (301).…”

A Distinctive Structural Twist in the Aminoimidazole Alkaloids from a Calcareous Marine Sponge: Isolation and Characterization of Leucosolenamines A and B

“…During recent expeditions to Papua New Guinea (PNG), specimens of the genus Leucosolenia (order Leucosolenida, family Lecucosoleniidae) were obtained and became high priority for further investigation because the crude MeOH extract showed positive activity in our primary screen for in vitro solid tumor selectivity. 14 Disclosed below are the results of this study culminating in the characterization two new compounds, leucosolenamines A (5) and B (6), possessing a 2-amino imidazole core substituted at C-4 and C-5, and the isolation of thymidine (7).…”

“…2 At the top of the list are natural products containing multiple chiral centers such as the bengamides, 3 fijianolides, 4 the halichondrin analogue E7389, 5 and the discodermolides 6 or sponge metabolites with exotic functionality, as in the psammaplins. 7 The research described in this paper began with the goal of adding additional unique structures to the rapidly growing list of sponge-derived alkaloids. In this regard, the Calcarea class of sponges is now recognized as a reliable source of richly bioactive metabolites possessing a 2-aminoimidazole 8 core that is often further substituted at the C-4 and C-5 positions.…”