Bromotyrosine-derived Metabolites Research Articles

Bromotyrosine-derived metabolites from an Indonesian marine sponge in the family Aplysinellidae (Order Verongiida).

Seven new bromotyrosine-derived metabolites, purpuramine M-N (1-2), araplysillin VII-XI (3-7) and six known compounds (8-13) were isolated from an Indonesian sponge belonging to the family Aplysinellidae (Order Verongiida). The structures of the new compounds were determined by extensive NMR experiments and mass spectrometric measurements. These compounds were screened against BACE1 and five cancer cell lines.

Concise Total Synthesis of Aplysinellamides A and B

Concise and efficient total syntheses of bromotyrosine-derived metabolites aplysinellamides A and B, isolated from Australian marine sponge Aplysinella sp., have been accomplished in seven steps. A condensation between cinnamic acid and Boc-D-lysine methyl ester was applied to form the amide skeleton as a key step.

Aplysinellamides A-C, bromotyrosine-derived metabolites from an Australian Aplysinella sp. marine sponge.

Mass-directed fractionation of an extract from the Australian marine sponge Aplysinella sp., from the Great Barrier Reef, resulted in the isolation of four new bromotyrosine derivatives, aplysinellamides A-C (1-3) and aplysamine-1-N-oxide (4), along with six known compounds (5-10). The structure elucidation of compounds 1-4 was based on their 1D and 2D NMR and MS spectroscopic data. Aplysamine-1 (6) increased the apolipoprotein E secretion from human CCF-STTG1 astrocytoma cells by 2-fold at the concentration of 30 μM.

Cytotoxic Psammaplysin Analogues from a Suberea sp. Marine Sponge and the Role of the Spirooxepinisoxazoline in Their Activity

Seventeen bromotyrosine-derived metabolites, including eight new compounds, were isolated from a Micronesian sponge of the genus Suberea. Four of the new compounds were psammaplysin derivatives (10-13), and the other four were ceratinamine derivatives (14-17). Of the compounds obtained, the psammaplysins exhibited cytotoxicity against human cancer cell lines (GI₅₀ values down to 0.8 μM), while the ceratinamine and moloka'iamine analogues showed almost no activity. These results suggest that the spirooxepinisoxazoline ring system is a requirement for cytotoxicity and, therefore, may serve as an attractive molecular scaffold for the development of a potent anticancer agent.

Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.

Chemical investigation of a southern Australian sponge, Pseudoceratina sp., resulted in the isolation of twelve bromotyrosine-derived alkaloids, comprising four new metabolites, aplysamine-7 (1), (−)-purealin B (2), purealin C (3) and purealin D (4); two new spiroisoxazole enantiomers, (−)-purealidin R (5) and (−)-aerophobin-2 (6); five known metabolites (−)-pseudoceratinine A (7), (−)-aeroplysinin-1 (8), aplysamine-2 (9), purpuramine G (10) and purpuramine J (11); and an artifact 12 derived from ethanolysis of 5. Structures for 1–12 were assigned on the basis of detailed spectroscopic analysis. A second southern Australian Pseudoceratina sp. afforded the first recorded account of a racemic bromotyrosine-derived spiroisoxazole, (±)-purealin (13b), together with the known achiral precursor purealidin A (15). A literature review of marine bromotyrosine-derived spiroisoxazoles reaffirmed the published dominance of (+)-spiroisoxazoles, acknowledging several accounts of (−)-spiroisoxazoles, while also revealing a wide range of chiroptical measurements suggestive of variable optical purity. The Pseudoceratina sp. metabolites 1–12, 13b and 15 were assessed for antibiotic properties, with the new metabolites 3 and 13b exhibiting broad spectrum activity against several Gram-positive bacteria.

11-Oxoaerothionin isolated from the marine sponge Aplysina fistularis shows anti-inflammatory activity in LPS-stimulated macrophages

Marine sponges of the order Verongida are a rich source of biologically active bromotyrosine-derived secondary metabolites. However, none of these compounds are known to display anti-inflammatory activity. In the present investigation, we report the anti-inflammatory effects of 11-oxoaerothionin isolated from the Verongida sponge Aplysina fistularis. When RAW264.7 cells and primary macrophages were preincubated with 11-oxoaerothionin and stimulated with LPS (lipopolysaccharide), a concentration-dependent inhibition of iNOS(inducible nitric oxide synthase) protein and NO-2 (Nitrite) production were observed. The same effect was observed when proinflammatory cytokines and PGE2 (Prostaglandin E2) production was evaluated. In summary, we demonstrated that in the presence of LPS, 11-oxoaerothionin suppresses NO2 and iNOS expression as well as inflammatory cytokines and PGE2.

Ianthelliformisamines A–C, Antibacterial Bromotyrosine-Derived Metabolites from the Marine Sponge Suberea ianthelliformis

A high-throughput screening campaign using a prefractionated natural product library and an in vitro Pseudomonas aeruginosa (PAO200 strain) assay identified two antibacterial fractions derived from the marine sponge Suberea ianthelliformis. Mass-directed isolation of the CH(2)Cl(2)/CH(3)OH extract from S. ianthelliformis resulted in the purification of three new bromotyrosine-derived metabolites, ianthelliformisamines A-C (1-3), together with the known natural products aplysamine 1 (4) and araplysillin I (5). The structures of 1-3 were determined following analysis of 1D and 2D NMR and MS spectroscopic data. This is the first report of chemistry from the marine sponge S. ianthelliformis. Ianthelliformisamine A (1) showed inhibitory activity against the Gram-negative bacterium P. aeruginosa with an IC(50) value of 6.8 μM (MIC = 35 μM).

Dereplication of Bromotyrosine-derived Metabolites by LC-PDA-MS and Analysis of the Chemical Profile of 14 Aplysina Sponge Specimens from the Brazilian Coastline

In order to investigate the chemical profile of 14 specimens of Aplysina spp. marine sponges, we have developed a method based on LC-PDA-MS for the detection of bromotyrosine-derived metabolites. The method enabled the dereplication of three distinct chemotypes of bromotyrosine-derived compounds based on UV absorptions, which were further refined by electrospray ionization-mass spectrometry analysis of the brominated quasi-molecular ion clusters. This procedure led to either a single compound assignment, or a maximum of two possible isobaric compounds. The dereplication study indicated that the chemical profile of the 14 specimens of Aplysina spp. analyzed presented practically the same dibromotyrosine-derived compounds. The results obtained suggested a possible biogenetic pathway for the formation of dibromotyrosine-derived compounds of wide occurrence in Verongida sponges.

Pseudoceratins A and B, Antifungal Bicyclic Bromotyrosine-Derived Metabolites from the Marine Sponge Pseudoceratina purpurea

Pseudoceratins A (1) and B (2) have been isolated from the marine sponge Pseudoceratina purpurea. Pseudoceratins are unique among the large class of bromotyrosine-derived sponge metabolites with respect to the substitution pattern of aromatic rings and the presence of spiroacetal and oxime ether functional groups as well as an 1,5-diamino-1,5-dideoxy-D-arabitol tether. Pseudoceratins A (1) and B (2) are epimeric differing in the orientation of the tether. Their structures were determined by analysis of spectral data. The rigidity of the compounds arising from their bridged structure gave ROESY/NOESY spectra with many transannular cross-peaks, which allowed the assignment of the relative stereochemistry of 1 and 2 to be established. The d-configuration of the 1,5-diamino-1,5-dideoxyarabitol unit was determined by converting the fragment isolated from the acid hydrolysate to the Mosher's ester and compared the 1H NMR spectrum with those of standard samples. Pseudoceratins exhibited significant antifungal activity against Candida albicans.

Two New Bromotyrosine‐Derived Metabolites from the Sponge Psammaplysilla purpurea

AbstractFor Abstract see ChemInform Abstract in Full Text.

Two new bromotyrosine-derived metabolites from the sponge Psammaplysilla purpurea.

Two new bromotyrosine-derived metabolites (1, 2) have been isolated along with the known compounds 3,5-dibromo-4-methoxyphenylacetonitrile, 3-bromo-4-methoxyphenylacetonitrile, 3-bromo-4-hydroxyphenylacetonitrile, 1-hydroxyuracil, 1-methoxyhemibastadin 2, purpuramine H and a steroid 5alpha,8alpha-epidioxycholest-6-en-3beta-ol from the sponge Psammaplysilla purpurea. Compounds 1 and 2 were characterized by interpretation of their spectral data. The antibacterial activity of these compounds is summarized.

Three new bromotyrosine derivatives lethal to crab from the marine sponge, Pseudoceratina purpurea

Three new bromotyrosine-derived metabolites, tokaradines A ( 1), B ( 2), and C ( 3), were isolated from the marine sponge Pseudoceratina purpurea. Their structures were determined by spectral methods. Tokaradines were lethal to the crab Hemigrapsus sanguineus.

Bromotyrosine-derived metabolites from the sponge Aiolochroia crassa

A chemical investigation of secondary metabolites from the sponge Aiolochroia crassa has been performed and five bromotyrosine derivatives ( 1–5) were identified. Their structures have been assigned on the basis of spectroscopic analysis, of which araplysillin III ( 2) and hexadellin C ( 3) possess new structures. The absolute configurations of dibromotyrosine moieties of 2 were determined by HPLC analysis of derivatized constituent amino acids obtained from acid hydrolysis. The stereochemistry of the spirocyclohexadienylisoxazoline moiety of compounds 1–3 was deduced from spectroscopic comparison of the same moiety of aerothionin, of which the absolute configuration was previously assigned by X-ray and CD analysis. Five bromotyrosine derivatives from the sponge Aiolochroia crassa have been identified. The structures including stereochemistry are reported for the new compounds ( 1) and ( 2). [Display omitted]

Three New Bromotyrosine-Derived Metabolites of the Sponge Psammaplysilla purpurea

Three new cytotoxic bromotyrosine-derived secondary metabolites, apylsamines 3 {2}, 4{3}, and 5{4}, were isolated from the sponge Psammaplysilla purpurea

Purpuramines A-I, new bromotyrosine-derived metabolites from the marine sponge Psammaplysilla purpurea

Nine new bromotyrosine-derived metabolites, purpuramines A∼I( 1∼9 and phenylpyruvic acid oxime ( 10) have been isolated from the marine sponge, Psammaplysilla purpurea. Their structures were determined by interpretation of spectral data. Compunds 1∼9 exhibited antibacterial activity against Staphylococcus aureus.

Two New Bromotyrosine-Derived Metabolites From an Australian Marine Sponge, Aplysina sp

Two new bromotyrosine-derived secondary metabolites, aplysamine-1 (5) and aplysamine-2 (6), were isolated from an Australian marine sponge, Aplysina sp. The structures were assigned on the basis of detailed spectroscopic analysis, and the tertiary amine salt character was revealed by conversion into the corresponding free tertiary amines. Cooccurring with (5) and (6) were the known antibiotic compounds (+)-aeroplysinin (1) and (3′,5′-dibromo-4′-ethoxy-1′-hydroxy-4′-methoxycyclohexa-2′,5′-dienyl)acetamide (2).