Bioactive Metabolites from the Caribbean Sponge Aka coralliphagum

Abstract

The chemistry of the burrowing sponge Aka coralliphagum was investigated to identify chemically labile secondary metabolites. The HPLC-MS analysis of the two growth forms typica and incrustans revealed different metabolites. The previously unknown sulfated compounds siphonodictyals B1 to B3 (6-8), corallidictyals C (9) and D (10), and siphonodictyal G (11) were isolated, and their structures were elucidated by NMR and MS experiments. The compounds were tested in a DPPH assay, in antimicrobial assays against bacteria, yeasts, and fungi, and in antiproliferation assays using cultures of mouse fibroblasts. The biological activity was linked to the presence of the ortho-hydroquinone moiety.The burrowing sponge Aka coralliphagum ()Siphonodictyon coralliphagum) is a bright yellow colored sponge that burrows into corals. Four distinct morphological growth forms have been described for Aka coralliphagum from the Caribbean: forma typica, f. tubulosa, f. obruta, and f. incrustans. 1 Several bioactive sesquiterpene hydroquinones, such as the siphonodictyals (B, 1) and siphonodictyols, 2 were obtained from the forms tubulosa and typica. Although the isolation of labile compounds such as siphonodictyols G (2) and H (3) suggested the existence of additional sulfated phenolic compounds in A. coralliphagum, compounds such as the siphonodictyals were isolated without respect to the occurrence of sulfated metabolites. Past isolation and purification methods did not account for the problem of compound hydrolysis. 2a,b This paper describes the isolation, structure elucidation, and biological testing of the new, labile metabolites siphonodictyals B1 to B3 (6-8), corallidictyals C (9) and D (10), and siphonodictyal G (11) from the Aka growth form incrustans. In order to compare the secondary metabolites of the two growth forms incrustans and typica, an HPLC analysis of their crude extracts was performed. These two forms of Aka occur in different habitats, with typica predominating on shallow water reefs (10-15 m) while incrustans occurs on deep water vertical slopes (20-25 m). It was deemed important to isolate the labile natural products of these two growth forms in their naturally occurring forms in order to understand more about their biological and ecological function. Results and DiscussionExtracts of sponge samples were investigated by an HPLC-MS screening. The two growth forms of Aka coralliphagum (typica and incrustans) showed differences in HPLC fingerprints and their major metabolites (Figure 1). While forma typica contained more polar compounds (shorter retention times), forma incrustans contained three main compounds with a less polar character. Further characterization by HPLC-API-CID-MS/MS showed a single or double sulfation of compounds with shorter retention times. This was deduced by loss of m/z 80 under MS/MS conditions and detection of a [SO 3 ] -ion at m/z 80 (see Supporting Information) 3 as well as a sulfur-specific isotopic pattern. These results indicate that the two growth forms have considerable differences...

Marine Sponges: Potential Sources of New Antimicrobial Drugs

“…The oxidation of hydroquinone to quinone and the hydrogenation of the side-chain increased the antibacterial effect of these molecules [74]. Other hydroquinones isolated in 2007 from the Caribbean sponge Aka coralliphaga showed activity against S. aureus [75], confirming the results of Sullivan et al [76].…”

Meroterpenes from Marine Invertebrates: Structures, Occurrence, and Ecological Implications

“…An aldehyde function is the distinctive feature of siphonodictyals A–D ( 123 – 126 ), G ( 127 ), B2 ( 128 ), and B3 ( 129 ), which have been isolated from Siphonodictyonspecies along with the relevant alcohols siphonodictyols G ( 130 ) and H ( 131 ) and siphonodictyoic acid ( 132 ); most of them were sulfated [100,101,102]. The isolated compounds were tested for antimicrobial activity (antibacterial, antifungal); it has been suggested that the different substituents on the aromatic moieties have an impact on activity and that the ortho -hydroquinone structure may be the active center of the molecules.…”

“…Structures with a fourth five-membered oxygen spiranic ring are cyclospongiaquinone-2 ( 193 ) [79,88], its analogs 7,8-dehydrocyclospongiaquinone-2 ( 194 ) and 9-epi-7,8-dehydrocyclospongiaquinone-2 ( 195 ) [89], and the corallidyctals A–D ( 196 – 199 ), isolated from the marine sponge Aka (= Siphonodictyon ) coralliphagum [102,143]. Both corallidictyal A ( 196 ) and B ( 197 ) inhibit PKC with an IC 50 = 28 μM, while assays addressing another cAMP-dependent kinase did not afford inhibition at concentrations of 300 μM, indicating its selectivity.…”

“…Both corallidictyal A ( 196 ) and B ( 197 ) inhibit PKC with an IC 50 = 28 μM, while assays addressing another cAMP-dependent kinase did not afford inhibition at concentrations of 300 μM, indicating its selectivity. Further, the assays revealed selectivity against the α isoform of PKC [102]. Corallidictyals C ( 198 ) and D ( 199 ) were tested in antiproliferative assays using cultures of mouse fibroblasts and activity was linked to the presence of the ortho -hydroquinone moiety [143].…”

Cytotoxic Terpene-Purines and Terpene-Quinones from the Sea

“…Further, the assays revealed selectivity against the α isoform of PKC. Corallidyctals C and D were tested in antiproliferative assays using cultures of mouse fibroblasts and activity was linked to the presence of the ortho-hydroquinone moiety [28]. Assays on cytotoxic activity were performed against P-388, A-549, HT-29 and MEL-28 cells and against the KB, Bel-7402, PC-3M, Ketr 3 and MCF-7 human tumour cell lines.…”