New Antifeedant Bromopyrrole Alkaloid from the Caribbean Sponge Stylissa caribica

Abstract

In this first report on the chemistry of the sponge Stylissa caribica, two known bromopyrrole metabolites and a new compound, N-methyldibromoisophakellin (1), were isolated and identified. The structure of 1 was determined using spectroscopic methods and the computer program COCON. N-Methyldibromoisophakellin (1) was shown to be the only secondary metabolite in Stylissa caribica that, at its natural concentration, is active as a feeding deterrent against a common omnivorous reef fish.In a recent survey of the chemical antipredatory defenses of 71 species of Caribbean sponges, it was discovered that all of the five species within the family Axinellidae yielded crude organic extracts that deterred the feeding of predatory reef fish in aquarium assays. 1 More recently it has been shown that one species, Axinella corrugata (previously Teichaxinella morchella), yielded high concentrations of stevensine as the single compound responsible for feeding deterrency. 2 The purpose of the study reported herein was to isolate and identify the metabolite(s) responsible for the chemical defense of Stylissa caribica, a sponge closely related to A. corrugata. To the best of our knowledge, this is the first report on the chemistry of S. caribica.A series of brominated pyrrole alkaloids have been isolated from a specimen of the sponge S. caribica collected off the coast of Sweetings Cay, Bahamas. Bioassay-guided fractionation of the methanol extract of this sponge resulted in the isolation of two known bromopyrrole-derived alkaloids, dibromoisophakellin (2, 13 mg) and ageliferin (3, 3 mg), as well as the new compound N-methyldibromoisophakellin (1, 140 mg). We describe herein the isolation, structural elucidation, and antifeedant properties against the common predatory reef fish Thalassoma bifasciatum of the new bromopyrrole alkaloid 1.The compounds 1-3 could be isolated using previously reported methods (details see Experimental Section and Supporting Information). The brominated alkaloids dibromoisophakellin (2) and ageliferin (3) Table 1). By comparison of δ C of 1 with all known intramolecular cyclized oroidin derivatives, the isophakellin skeleton was obtained. 4 Therefore, the structure of 1 was identified and confirmed by COCON 5 as the N-methyl derivative of dibromoisophakellin (2). The absolute configuration of 1 was determined by comparison of the optical rotation of 1 with that of 2. 3a Since recent studies 6 have found no evidence for structural or nutritional defenses, deterrent metabolites appear to be the principal defensive strategy of Caribbean sponges against predatory reef fishes. To investigate the feeding deterrency of the major metabolite of S. caribica, aquarium assays were performed using previously reported methods. 7 When incorporated into artificial foods at the same volumetric concentration as found in sponge tissue (0.9 mg/mL), N-methyldibromoisophakellin (1) deterred

Stylissamides A–D – New Proline‐Containing Cyclic Heptapeptides from the Marine Sponge Stylissa caribica

“…[13] The ∆δ βγ of Pro 1 and Pro 4 were both 3.5 ppm and that of Pro 5 was 9.5 ppm. This indicated a trans configuration for Pro 1 and Pro 4 and a cis configuration for Pro 5 . The NOE correlation Pro 4 -Hα/ Table 3).…”

“…[5] Using HPLC-HRMS screening of the crude extract several new metabolites were isolated: 4-bromopyrrole-2-carboxy-N(ε)-lysine, [6] 4-bromopyrrole-2-carboxyarginine, [6] oxocyclostylidol, [7] and stylissadines A and B. [8] In the course of this investigation a Sephadex LH-20 fraction of the n-butanol phase was analyzed.…”

Chemical defense against predators and bacterial fouling in the Mediterranean sponges Axinella polypoides and A. verrucosa

“…In the latter study, found 2 exceptions to the general rule: the Red Sea sponge Axinella carteri and a Caribbean Stylissa species, both belonging to the family Axinellidae. These 2 species are known to contain bromopyrrole compounds including feeding-deterrent ones (Fedoreyev et al 1986, Assmann et al 2001b, Assmann & Köck 2002, Ortlepp et al 2007, and thus might rely on chemical anti-predator defense alone. Ferguson & Davis (2008) indicated the possibility that spicules of a size smaller than 100 µm deter the generalist sea urchin Centrostephanus rodgersii.…”

Sitotoksisitas Invertebrata Laut sebagai Biomarker Lingkungan di Kawasan Konservasi Perairan Pulau Banda

“…Biota ini mengandung senyawa bioaktif yang mampu menghambat pertumbuhan sel lestari tumor paling tinggi. Penelaahan pustaka menemukan bahwa genus Stylissa memiliki ciri metabolit berupa senyawa alkaloid terbrominasi (Assmann, Van Soest & Köck, 2001). Penelitian bioaktivitas spons Stylissa sp.…”

“…dari wilayah perairan konservasi Karimunjawa (Jawa Tengah) sebelumnya telah menemukan senyawa halogenasi hymeniadisine, 3-bromo dimeniadiside, dan dibromophakelin (Januar, Wikanta, Fajarningsih & Sugiyono, 2006;Januar, Motti, Tapiolas & Wright, 2009). Selain itu, berbagai senyawa halogenasi nitrogen lainnya, misalnya bromopyrrole alkaloid, brominated pyrrole-2-aminoimidazole alkaloids, dan dispacamide juga telah dilaporkan dari jenis biota ini (Assmann et al, 2001;Ebada et al, 2015;Yarnold et al, 2012). Kelompok alkaloid terbrominasi telah diketahui memili ki sif at f armakologis untuk sitotoksisitas terhadap sel tumor, antibakteri, dan antifungi (Dembitsky, 2002).…”