Cyclic Heptapeptides from the Jamaican Sponge Stylissa caribica

Abstract

Two new cyclic heptapeptides, stylisin 1(1) and stylisin 2 (2), were isolated and characterized from the Jamaican sponge Stylissa caribica, in addition to the cyclic heptapeptide phakellistatin 13 (3) and the known bromopyrrole alkaloids sceptrin (4), stevensine (5), and oroidin (6). The new structures were assigned on the basis of 1D and 2D NMR spectroscopic data, as well as chemical methods for the elucidation of the absolute configuration of amino acids. The peptides and alkaloids have been evaluated for their antimicrobial, antimalarial, anticancer, anti-HIV-1, antiMtb, and antiinflammatory activities.Peptides are well-established bioactive metabolites from marine invertebrates , and include linear peptides, , depsipeptides, , and cyclic -and bicyclic peptides. , Species of the sponge genera Phakellia and Axinella have yielded several bioactive cyclic peptides -reported to have cytotoxic activity against a number of cancer cell lines. It has been noted that most of these cyclic peptides are rich in proline amino acid moieties, which may be in either cis or trans conformation. There is evidence that some of the sponge cyclic peptides are able to bind undetectable quantities of a very potent antineoplastic substance that can only be revealed through biological assays.In this report as part of an investigation of active sponge extracts against infectious diseases two new cyclic heptapeptides, stylisin 1 (1) and stylisin 2 (2), and the known peptide phakellistatin 13 (3) were isolated as well as the known alkaloids sceptrin (4), stevensine (5), and oroidin (6). Here we describe the isolation and structure elucidation of the two new cyclic peptides. Several reports describing the chemistry of different marine sponges belonging to Stylissa spp. have been published including aldisines from Stylissa massa, latonduines from Stylissa carteri, and massadine from Stylissa aff. massa. In a study regarding the chemistry of Stylissa caribica Lehnert & van Soest, 1998 (Halichondrida: Dictyonellidae), a series of bromopyrrole alkaloids have been identified. No cyclic peptides have been previously reported from Stylissa species, and these results have suggested a possible microbial or symbiotic origin for these metabolites. HHS Public Access Results and DiscussionThe sponge extract was dissolved in ethanol and subjected to silica gel vacuum-liquid chromatography followed by column chromatography, Sephadex LH-20, RP HPLC, and PTLC chromatography to yield two new cyclic heptapeptides, stylisin 1 (1) and stylisin 2 (2), the known cyclic peptide phakellistatin 13 (3), and the known alkaloids sceptrin, stevensine, and oroidin (4-6).Stylisin 1 (1) ( (Figures 2 and 3). Each amino acid was connected to the adjacent amino acid in a cyclic form based on the HMBC correlations between the αH and NH with the adjacent CO. An HMBC correlation was assigned between the isoleucine NH and CO of Pro1 at δ 171.48 and generated a partial structure for a Pro1-Ile. The amide proton at δ 7.44 of Phe gave an HMBC correlation to CO of ...

Spatial Variability in Secondary Metabolites of the Indo-Pacific Sponge Stylissa massa

“…Stylissa massa belongs to the family Dictyonellidae, which is one of the better investigated groups of marine invertebrates from the perspective of natural products chemistry, and some of the identified compounds have known ecological roles (Becerro et al, 2003). The most prominent natural products isolated from S. massa include the alkaloids oroidin, debromohymenialdisine, hymenialdisine (Tasdemir et al, 2002), sceptrin (Mohammed et al, 2006), hymenidin (Kobayashi et al, 1986), and palau'amine (Kinnel et al, 1993). The aim of this study was to assess the variation in secondary metabolite production in S. massa at various spatial scales, including local, regional, and biogeographic.…”

Bromopyrrole alkaloids from the caribbean sponge Agelas cerebrum

“…7 Sceptrin was evaluated against D6 and W2 strains by other authors and showed no activity. 32 In conclusion, this chemical study underscores the presence of bromopyrrole alkaloids as the representative secondary metabolites of Agelas cerebrum, and contributes to the chemotaxonomy within the Agelasidae family. Studies are in progress in order to advance the evaluation of the in vivo antimalarial activity of bromopyrrole alkaloids from Agelas cerebrum.…”

High resolution spatial mapping of brominated pyrrole-2-aminoimidazole alkaloids distributions in the marine sponge Stylissa flabellata via MALDI-mass spectrometry imaging

“…The pseudomolecular ion cluster for the compound at m/z 825/ 827/829/831/333/835 was indicative of a chlorotetrabrominated compound. There are at least two B-P-2-AI compounds published with this molecular weight: konbu'acidin B 3 (8) and tetrabromostyloguanidine (9). 33 MS-MS analysis of this ion cluster obtained directly from the tissue slice yielded fragments 18, 251 and 269 amu smaller than the parent indicating loss of water, a dibromopyrrole carboxylate and water and dibromopyrrole carboxylate respectively.…”