Njaoamines A-F, new cytotoxic polycyclic alkaloids from the haplosclerid sponge Reniera sp.

Six new cytotoxic polycyclic alkaloids containing an 8-hydroxyquinoline moiety, njaoamines A-F (1-6), have been isolated from the 2-propanol extract of the sponge Reniera sp. collected in Tanzania. Their structures were determined by extensive analysis of their spectroscopic features, particularly 1D and 2D NMR spectra recorded in Py-d₅. Cytotoxicity of the compounds isolated was evaluated against a panel of three human tumor cell lines.     

Diazonamides C-E, new cytotoxic metabolites from the ascidian Diazona sp.

Three new macrocyclic peptides, diazonamides C-E (1-3), were isolated together with the previously reported diazonamides A (4) and B (5) from samples of the marine ascidian Diazona sp. collected in Indonesia. Their structures were assigned on the basis of detailed analysis of the 1D and 2D NMR and mass spectral data as well as Marfey’s analysis of the aminoacid residues. All the new compounds isolated displayed moderate cytotoxicity against a panel of three human tumor cell lines.     

Violatinctamine, a new heterocyclic compound from the marine tunicate Cystodytes cf. violatinctus

A new alkaloid designated violatinctamine and four known metabolites were isolated from the tunicate Cystodytes cf. violatinctus collected in Kenya. Violatinctamine has a unique heterocyclic skeleton, which combines a benzothiazole unit and a dihydroisoquinoline unit. The structure of violatinctamine was elucidated by interpretation of MS results as well as 1D and 2D NMR spectra of the alkaloid and of its O,O′-dimethyl derivative. Analysis of the spectral information also implies that violatinctamine exists as a mixture of two tautomers—the imino-phenol and the amino quinone-methide.     

New cytotoxic spongian diterpenes from the sponge Dysidea cf. arenaria

Seven new (1-7) and three known (8-10) spongian-class diterpenes have been isolated from the sponge Dysidea cf. arenaria collected in Okinawa. Compound 6 was also isolated from the nudibranch Chromodoris kuniei. The structures of the new entities were elucidated by spectroscopic analyses. Three of the new spongians (2, 6, and 7) showed cytotoxicity against NBT-T2 rat bladder epithelial cells.     

Njaoamine I,a cytotoxic polycyclic alkaloid from the Haplosclerida sponge Haliclona (Reniera) sp.

A new cytotoxic polycyclic alkaloid containing a quinoline moiety, njaoamine I (1) has been isolated from the methanol extract of the sponge Haliclona (Reniera) sp. collected at Okuza Island, Tanzania. The structure of compound 1 was determined by 1D and 2D NMR and HRMS data analysis. Its relative configuration was elucidated by a NOESY experiment and confirmed by comparison of its NMR spectral data to those of njaoamines A–H. Moreover, njaoamine G (2) was also detected by LC/MS analysis of the methanol extract. Njaoamine I (1) displays cytotoxic activity against a panel of three human tumor cell lines in the micromolar range.     

Ishigadine A,a new canthin-6-one alkaloid from an Okinawan marine sponge Hyrtios sp.

A new indole alkaloid with the canthin-6-one skeleton, ishigadine A, has been isolated from an Okinawan marine sponge Hyrtios sp. The structure of ishigadine A was elucidated on the basis of spectroscopic analyses. Ishigadine A is a new canthin-6-one alkaloid possessing a hydroxy group, a 1,3-dimethyl-4-methylthioimidazolium, and a 1-propylguanidine. Ishigadine A is the third canthin-6-one alkaloid from sponges. Ishigadine A might be generated from l-arginine, l-histidine, and l-tryptophan. Ishigadine A exhibited moderate cytotoxicity against L1210 murine leukemia cells.     

Miyakosynes A-F, cytotoxic methyl branched acetylenes from a marine sponge Petrosia sp.

Cytototoxic linear acetylenes, miyakosynes A-F, were isolated from a marine sponge Petrosia sp. Their structures were elucidated by a combination of spectroscopic analyses and chemical methods. The absolute configuration of the secondary alcohols at each terminus was determined by the modified Mosher’s analysis. Miyakosynes show cytotoxicity against HeLa cells at submicromolar concentrations.     

Botryllamides K and L, new tyrosine derivatives from the Australian ascidian Aplidium altarium

Chemical investigation of the Australian ascidian Aplidium altarium led to the isolation of two new tyrosine derivatives, botryllamides K (1) and L (2), together with six known metabolites, botryllamides A-C (3-5), botryllamide G (6) and perspicamides A (7) and B (8). The structures of these compounds were elucidated by spectroscopic analysis. This is the first reported chemistry from this species. Compounds 1-8 were evaluated for their cytotoxicity towards the tumour cell lines, MCF-7 (breast), H460 (lung) and SF268 (central nervous system).     

Cebulactams A1 and A2, new macrolactams isolated from Saccharopolyspora cebuensis, the first obligate marine strain of the genus Saccharopolyspora

The new macrolactams cebulactams A1 and A2 were isolated from an extract of the first obligate marine strain of the genus Saccharopolyspora. Their constitutionally identical structures, each bearing a six-membered cyclic ether as part of the macrocycle, and their relative configurations were elucidated by MS methods and by 1D and 2D NMR techniques.     

Fascioquinols A-F: bioactive meroterpenes from a deep-water southern Australian marine sponge, Fasciospongia sp.

Chemical investigation of a southern Australian deep-water marine sponge, Fasciospongia sp., returned the new meroterpene sulfate fascioquinol A (1) together with a series of acid mediated hydrolysis/cyclization products, fascioquinols B (2), C (3) and D (4), and strongylophorine-22 (5). Additional co-metabolites include the new meroterpenes fascioquinol E (6) and fascioquinol F (8), together with the known sponge metabolite geranylgeranyl 1,4-hydroquinone (7). Structures were assigned to 1-8 on the basis of detailed spectroscopic analysis, chemical interconversion, mechanistic and biosynthetic considerations, and literature comparisons. The known 1,4-hydroquinone 7 was identified as the dominant cytotoxic principle in the Fasciospongia sp. extract, with selective inhibitory activity against gastric adenocarcinoma (AGS, IC₅₀ 8 μM) and neuroblastoma (SH-SY5Y, IC₅₀ 4 μM) cell lines. By contrast, while the fascioquinols displayed little or no inhibitory activity towards human cell lines, 1 and 2 displayed promising Gram-positive selective antibacterial activity towards Staphylococcus aureus (IC₅₀ 0.9-2.5 μM) and Bacillus subtilis (IC₅₀ 0.3-7.0 μM).     

Caldorin,a new polyketide from the marine cyanobacterium Caldora penicillata

A new polyketide with a cis-fused decalin ring scaffold, caldorin, was isolated from the marine cyanobacterium Caldora penicillata. The gross structure and relative configuration were elucidated by spectroscopic analyses. We also clarified that caldorin is a weak SOAT inhibitor and moderate osteoblast differentiation inhibitor. On the other hand, caldorin did not exhibit cytotoxicity against either HeLa or HL60 cells.     

Njaoamines G and H, two new cytotoxic polycyclic alkaloids and a tetrahydroquinolone from the marine sponge Neopetrosia sp.

Two new polycyclic alkaloids, njaoamines G (1) and H (2) and 1,2,3,4-tetrahydroquinolin-4-one (3) have been isolated from the sponge Neopetrosia sp. collected at Pemba Island, Tanzania. Compounds 1 and 2 are close in structure to njaoamines A-F. Compound 3, known synthetically, is a new natural compound. The structures and relative stereochemistries of compounds 1 and 2 were elucidated on the basis of spectroscopic data. Njaoamines G and H are potent brine shrimp toxins with LD₅₀ values of 0.17 μg/mL and 0.08 μg/mL for 1 and 2, respectively.     

Poecillastrin E,F, and G,cytotoxic chondropsin-type macrolides from a marine sponge Poecillastra sp.

Poecillastrin E (1), F (2), and G (3) were isolated from a marine sponge Poecillastra sp. as the cytotoxic constituents. Their planar structures were determined by analyzing the MS and NMR spectra. They are closely related to the known poecillastrin C (4). The absolute configuration of the β-hydroxyaspartic acid (OHAsp) residue was determined to be D-threo by Marfey's analysis of the hydrolysate. The mode of lactone ring formation of OHAsp residue in 1–3 was determined by selective reduction of the ester linkage followed by acid hydrolysis.     

Mycapolyols A-F, new cytotoxic metabolites of mixed biogenesis from the marine sponge Mycale izuensis

[structure: see text]. Mycapolyols A-F (1-6), six new unusual PKS/NRPS metabolites, were isolated from the marine sponge Mycale izuensis. The gross structures were elucidated by analysis of spectroscopic data, while the stereochemistry was established using chemical method and the universal NMR database.     

Rakanmakilactones A-F, new cytotoxic sulfur-containing norditerpene dilactones from leaves of Podocarpus macrophyllus var. maki

Six new S-containing norditerpene dilactones, rakanmakilactones A-F (5-10), were isolated from the leaves of Podocarpus macrophyllus D. Don var. maki Endl., along with four known norditerpene dilactones (1-4). Their structures, stereochemistry and absolute configurations were determined by spectroscopic studies (HRMS, IR, ¹H, ¹³C and 2D NMR), and single-crystal X-ray analyses. Rakanmakilactones were found to have a cytotoxic effect against P388 murine leukemia cells.     

Axiplyns A-E, new sesquiterpene isothiocyanates from the marine sponge Axinyssa aplysinoides

Five new isothiocyanate sesquiterpenes, designated axiplyns A-E (1-5) have been isolated, together with two known isothiocyanate sesquiterpenes (6, 7), from the sponge Axinyssa aplysinoides collected at Misali Island, Tanzania. Axiplyns 4 and 5 embody a new indane sesquiterpene skeleton, and compounds 1, 2, and 5 contain unprecedented ring systems, namely a 6,8-dioxabicyclo[3.2.1]octane and a 2-oxabicyclo[2.2.1]heptane. Axiplyns A, B, and C are potent brine shrimp toxins with LD₅₀ values between 1.5 and 1.8 μg/mL.     

Exiguolide, a new macrolide from the marine sponge Geodia exigua

A new 20-membered macrolide designated exiguolide has been isolated from the marine sponge Geodia exigua, and its structure determined by interpretation of spectroscopic data. Exiguolide specifically inhibited fertilization of sea urchin (Hemicentrotus pulcherrimus) gametes but not embryogenesis of the fertilized egg.     

Caldaphnidines A-F, six new Daphniphyllum alkaloids from Daphniphyllum calycinum

Six new Daphniphyllum alkaloids, namely caldaphnidines A-F (1-6), together with eight known ones, deoxycalyciphylline B, deoxyisocalyciphylline B, bukittiggine, calycicine A, methyl homosecodaphniphyllate, daphnilactone B, and daphnezomines L-M, were isolated from the leaves and the seeds of Daphniphyllum calycinum. The structure of 1 was determined by a single-crystal X-ray diffraction study, and the structures of 2-6 were established by spectral methods, especially two-dimensional NMR techniques (¹H-¹H COSY, HMQC, HMBC, and NOESY).     

Diplopuupehenone, a new unsymmetrical puupehenone-related dimer from the marine sponge Dysidea sp.

A new unsymmetrical puupehenone-related dimer, diplopuupehenone, comprising puupehenone and puupehenol segments, was isolated from the marine sponge Dysidea sp., along with the known metabolites, puupehenone and bispuupehenone. The structure of diplopuupehenone was established from spectroscopic data and by spectroscopic analysis of an acetoxy derivative. Diplopuupehenone showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with an IC₅₀ value of 8 μM.     

Lyngbyacyclamides A and B, novel cytotoxic peptides from marine cyanobacteria Lyngbya sp.

Lyngbyacyclamides A (1) and B (2), novel cyclic peptides, were isolated from marine cyanobacteria Lyngbya sp. collected in Okinawa, Japan. Their structures were determined by spectroscopic analyses and degradation studies. They moderately inhibited the growth of B16 mouse melanoma cells.