Sceptrin

Abstract: Biologically active extracts of the Caribbean sponge Agelas conifera have yielded, in exhaustive studies, the diacetate salts of seven new bromopyrroles (1,3-8), as well as that of the known debromooroidin dimer sceptrin (2). These compounds were found to be antiviral and antibacterial and were active in barnacle settlement and biochemical prophage induction assays. The structures assigned were based on spectroscopic comparisons to sceptrin and two-dimensional NMR data. Synthetic bromopyrroles were used to verify bromine substitution patterns. The oxysceptrins (4,5) are characterized by their aminoimidazolinone group, the ageliferins (6-8) by a unique cyclohexene-based skeleton

Abstract: Previous studies have determined that Caribbean reef sponges of the genus Agelas are chemically defended from fish predation by brominated pyrrole alkaloids, and that the compounds responsible for this defense have been elucidated for 1 species, A. clathrodes. In this study, we ex- pand our understanding of chemical defense in this common sponge genus to include the character- ization of defensive metabolites in the tissues of A. wiedenmayeri and A. conifera. Bioassay-directed isolation of defensive metabolites was undertaken using fish feeding assays carried out in laboratory aquaria and in the field. A. wiedenmayeri contained the same 2 major metabolites as A. clathrodes, 4, 5-dibromopyrrole-2-carboxylic acid (1), and oroidin (2), in addition to a small amount of bromoage- liferin (7). The 2 major metabolites were present at higher concentrations in samples of A. wieden- mayeri than in A. clathrodes, and their relative concentrations were reversed, with A. wiedenmayeri on average containing more 4,5-dibromopyrrole-2-carboxylic acid (1) (2.0 mg ml -1 ) than oroidin (2) (0.8 mg ml -1 ). A. conifera contained a mixture of dimeric bromopyrrole alkaloids dominated by scep- trin (3), with <10% each of dibromosceptrin (5), bromoageliferin (7), dibromoageliferin (8), ageliferin (6), and bromosceptrin (4). Mean concentration of sceptrin (3) in sponge tissue was 5.3 mg ml -1 ; this compound deterred feeding of reef fish in aquarium assays at 1.0 mg ml -1 , the lowest concentration assayed. Sceptrin (3) concentrations were higher in sponges collected in the southern Bahama Islands than in those collected in the middle Bahamas, but the reasons for this variation remain unclear. The structure-activity relationship of the pyrrole group was investigated by assaying derivatives of the active metabolites. Feeding deterrent activity of the molecule was enhanced by the addition of bro- mine to the pyrrole group, but not affected by exchange of the heteroatom from N to O or S. Com- bining an understanding of the structure-activity relationship of Agelas metabolites with an under- standing of the variation in these metabolites across the genus may provide insight into the evolution of defensive chemistry in this highly successful taxa of pan-tropical sponges.

Abstract: In the present study,13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau’amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin A (13), and agelongine (14), obtained from marine sponges belonging to Axinella and Agelas generahave been screened in vitro against four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania donovani and Plasmodium falciparum (K1 strain, a chloroquine resistant strain), responsible of human diseases with high morbidity and, in the case of malaria, high mortality. Our results indicate longamide B (8) and dibromopalau’amine (11) to be promising trypanocidal and antileishmanial agents, while dispacamide B (3) and spongiacidin B (6) emerge as antimalarial lead compounds.In addition,evaluation of the activity of the test alkaloids (2–14) against three different enzymes (PfFabI, PfFabG, PfFabZ) involved in the de novo fatty acid biosynthesis pathway of P. falciparum (PfFAS-II) identified bromopyrrolohomoarginin (12) as a potent inhibitor of PfFabZ. The structural similarity within the series of tested molecules allowed us to draw some preliminary structure-activity relationships. Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids.

Abstract: Attachment is one of the first steps in bacterial colonization. By inhibiting bacterial attachment on surface cells, sponges may not only prevent infection, but also the process of biofoul- ing. Crude organic extracts from 26 species of Caribbean sponges were assayed for their ability to inhibit bacterial attachment. Bacterial attachment was tested using Vibrio harveyi, a motile marine bacterium, isolated from seawater collected above one of the reefs from which sponges were sampled. Extracts were incorporated into agar blocks at concentrations volumetrically equivalent to whole sponge tissue. Extracts from 21 of 26 species (81%) resulted in bacterial attachment on treated blocks that was <40% of attachment on controls. Of these extracts, 9 were particularly active, with mean levels of attachment < 8% of controls (Agelas conifera, Ailochroia crassa, Aka coralliphagum, Amphimedon compressa, Aplysina fulva, Erylus formosus, Plakortis halichondroides, Ptilocaulis spiculifera, Verongula gigantea). Extracts from 4 species (Ailochroia crassa, Chondrilla nucula, Ectyoplasia ferox, and Iotrochota birotulata) inhibited bacterial attachment in this assay but were not found to inhibit bacterial growth in a previous study. Purified compounds that deterred feeding of predatory fishes in a prior study were also tested for their effects on bacterial attachment; they were: oroidin, 4,5-dibromopyrrole-2-carboxylic acid and sceptrin from Agelas species, amphitoxin from A. compressa, aeroplysinin-1 and dibromocyclohexadienone from Aplysina species, steroidal glycosides from E. ferox, and formoside from E. formosus. Of these, all but the steroidal glycosides from E. ferox deterred bacterial attachment at natural concentrations, providing evidence that sponge secondary metabolites may have multiple ecological functions.