Cyclic tetrapeptides from marine bacteria associated with the seaweed Diginea sp. and the sponge Halisarca ectofibrosa

A Pseudomonas sp. was cultured which was associated with the Japanese seaweed Diginea sp. Crude extracts prepared from this bacterial culture were found to inhibit the growth of other marine bacterial strains. From this bacterial culture, two new peptides cyclo-[phenylalanyl-prolyl-leucyl-prolyl] (3) and cyclo-[isoleucyl-prolyl-leucyl-alanyl] (4) have been isolated together with two known peptides (1) and (2). The crude extract from a culture of Pseudoalteromonas sp. associated with the Thai sponge Halisarca ectofibrosa was found to inhibit the growth of Bacillus subtilis and Vibrio anguillarum. Isolation studies yielded a fraction containing two peptides that were identified as cyclo-[phenylalanyl-leucyl]₂ (5) and cyclo-[leucyl-isoleucyl]₂ (6) by means of LC-MS and 2D NMR data. Absolute stereochemistry was confirmed by the synthesis of cyclo-[l-phenylalanyl-l-leucyl]₂. Peptides (1)-(3) were also isolated from this bacterial strain. None of the individual peptides isolated in this study showed antibiotic activity.     

Isolation and synthesis of N-acyladenine and adenosine alkaloids from a southern Australian marine sponge, Phoriospongia sp.

Chemical fractionation of the southern Australian marine sponge Phoriospongia sp. (CMB-03107) yielded phorioadenine A (1) as a nematocidal agent and the first reported example of a 6-N-acyladenine natural product. The structure of 1 was confirmed by spectroscopic analysis and the chemical synthesis of racemic (1a) and enantiomeric (1b) analogues. HPLC–ESIMS analysis of the crude sponge extract with comparisons to the synthetic 6-N-acyladenosine 2a provided evidence that the biosynthetically related adenosine, phorioadenosine A (2), was present as a trace co-metabolite. The rare starfish metabolite asterubine (3) was also isolated as a co-metabolite, and its structure confirmed by spectroscopic analysis and chemical synthesis. Biological investigations confirmed that natural products 1–3 and synthetic analogues 1a–e and 2a were not cytotoxic to multiple mammalian cancer cell lines, or Gram-positive or -negative bacteria. Nematocidal activity (inhibition of larval development of Haemonchus contortus) detected in the Phoriospongia sp. extract was attributed to 1 (LD₉₉ 31 μg/mL), with preliminary structure–activity relationship investigations confirming the importance of the N-acyl side chain.     

Topsentiasterol sulfates with novel iodinated and chlorinated side chains from the marine sponge Topsentia sp.

Three new marine polar steroids, the first chlorine-containing steroid sulfate (1), topsentiasterol sulfate F (2) and the first natural iodinated steroid (3) have been isolated from the marine sponge Topsentia sp. The structures of 1-3 were elucidated using NMR and HRESIMS as well as by chemical correlation of 1 with previously known topsentiasterol sulfate D. Compound 1 proved to be an effective inhibitor of endo-1,3-β-d-glucanase from the marine mollusc Spisula sachalinensis.     

Halichonadins A-D, new sesquiterpenoids from a sponge Halichondria sp.

A new dimeric sesquiterpenoid with two eudesmane skeletons through a urea linkage, halichonadin A (1), as well as three new eudesmane sesquiterpenoids having a carbamate, an isonitrile, or an amino functionality, halichonadins B (2), C (3), and D (4), respectively, have been isolated from a marine sponge Halichondria sp., and the gross structures and relative stereochemistry of 1-4 were elucidated on the basis of spectral data and chemical means.     

Sesquiterpenoids with PPARδ agonistic effect from a Korean marine sponge Ircinia sp.

One monocyclofarnesol-derived sesquiterpenoid (1), four new meroterpenoids (2–5) as well as two isolation artifacts (6–7) and a known sesquiterpenoid (8) were isolated from the marine sponge Ircinia sp. Their chemical structures were elucidated via analyses of spectroscopic data, which included NMR and HRMS data. Two terpenoids, 1 and 4, showed PPARδ agonistic activities, with EC₅₀ values of 18 and 30 μg/mL, respectively.     

Halichonadins G-J, new sesquiterpenoids from a sponge Halichondria sp.

Three new dimeric sesquiterpenoids, halichonadins G-I (1-3), and one new eudesmane sesquiterpenoid possessing a 1-phenethyl urea moiety, halichonadin J (4), were isolated from a marine sponge Halichondria sp. Halichonadins G (1) and H (2) are homo-dimers of eudesmane sesquiterpenoid, linked through a methyl 2-{1-(2-amino-2-oxoethyl)ureido}acetate fragment and a 2-hydroxymalonamide fragment, respectively, while halichonadin I (3) is a new hetero-dimer of eudesmane sesquiterpenoid linked through a urea fragment. The structures of 1-4 were elucidated on the basis of spectroscopic data.     

N-Hydroxypyridone alkaloids,chromone derivatives,and tetrahydroxanthones from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248

Six new compounds, an N-hydroxypyridone glucoside, orbiocrellin A (1), its aglycone orbiocrellin B (2), chromone glucosides 3 and 4, a dihydrochromone 5a/5b, and a chromone 6, were isolated from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248. Orbiocrellin A (1) exhibited antimalarial activity against Plasmodium falciparum K1 (IC₅₀ 3.1 μg/mL) while it was non-cytotoxic. In contrast, orbiocrellin B (2) showed both antimalarial (IC₅₀ 2.1 μg/mL) and cytotoxic (NCI-H187 cells, IC₅₀ 0.70 μg/mL) activities.     

Metachromins L-Q, new sesquiterpenoid quinones with an amino acid residue from sponge Spongia sp.

Six new sesquiterpenoid quinones with an amino acid residue, metachromins L-Q (1-6), have been isolated from an Okinawan marine sponge Spongia sp. The structures and stereochemistry of 1-6 were elucidated on the basis of the spectroscopic data and chemical correlations. Metachromins L (1) and M (2) showed modest cytotoxicity.     

Karatungiols A and B, two novel antimicrobial polyol compounds, from the symbiotic marine dinoflagellate Amphidinium sp.

Karatungiols A (1) and B (2), two novel antimicrobial polyol compounds, were isolated from the cultivated symbiotic marine dinoflagellate Amphidinium sp. Their structures were elucidated based on spectroscopic analysis and degradation reactions. Karatungiols A (1) and B (2) consisted of a C69-linear chain with a ketone moiety, 24 or 25 hydroxyl groups, and two tetrahydropyran rings. Karatungiol A (1) exhibited antifungal activity against Aspergillus niger at 12 μg/disc and antiprotozoan activity against Trichomonas foetus at 1 μg/ml.     

Kendarimide A, a novel peptide reversing P-glycoprotein-mediated multidrug resistance in tumor cells, from a marine sponge of Haliclona sp.

A novel modulator of multidrug resistance (MDR) in tumor cells, kendarimide A (1), was isolated from an Indonesian marine sponge of Haliclona sp. Compound 1 reversed MDR in KB-C2 cells mediated by P-glycoprotein (P-gp) at a 6 μM concentration, and the chemical structure of 1 was characterized to be a linear peptide composed of N-methylpyroglutamic acid (pyroMeGlu), N-methylated eight-membered cysteinyl-cysteine (ox-[MeCys-MeCys]) together with many N-methyl amino acid residues. The amino acid sequence of 1 was determined by 2D NMR and FAB MS analysis. The absolute configuration of the amino acid residues in 1 except for the MeCys part was determined to be l-form respectively, based on interpretation of the HPLC analysis of Marfey's derivatives of the hydrolysates of 1 and the synthetic method for the pyroMeGlu residue.     

Jaspolides G and H, unique bisisomalabaricanes from the Chinese marine sponge Jaspis sp.

Two unique bisisomalabaricanes jaspolides G (1) and H (2) were isolated from the marine sponge Jaspis sp. Their structures were elucidated on the basis of extensive spectroscopic data (IR, MS, and 1D and 2D NMR) analyses. A possible biogenetic pathway via Diels-Alder dimerization for jaspolides G and H was also proposed.     

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).     

Agelasines O-U, new diterpene alkaloids with a 9-N-methyladenine unit from a marine sponge Agelas sp.

New diterpene alkaloids, agelasines O-U (1-7), have been isolated from an Okinawan marine sponge Agelas sp. The gloss structures and relative stereochemistries of 1-7 were elucidated from the spectroscopic data. Agelasines O-R (1-4) were the third examples of diterpene alkaloid with a 9-N-methyladenine and a pyrrole units. Agelasine O (1) has a halimane skeleton, while agelasines P-R (2-4) have a clerodane skeleton. Agelasines S-U (5-7) were new diterpene alkaloids with a 9-N-methyladenine unit consisting of a halimane skeleton, a labdane skeleton, and a clerodane skeleton, respectively. Agelasines O-R (1-4) and T (6) showed antimicrobial activities against several bacteria and fungi.     

Lissoclibadins 1-3, three new polysulfur alkaloids, from the ascidian Lissoclinum cf. badium

Three new polysulfur alkaloids, lissoclibadins 1 (1)-3 (3), were isolated from the ascidian Lissoclinum sp. (cf. L. badium Monniot, F. and Monniot, C., 1996). The structures of 1-3 were assigned on the basis of their spectral data, and the computational modeling study was utilized for 1. Compound 1 had a trimeric structure of three identical aromatic anime moieties connected through two sulfide and a disulfide bonds. Compounds 2 and 3 were dimeric structures of the same unit as that of 1 connected through a sulfide and disulfide bonds (2) and two sulfide bonds (3). Compounds 1 and 2 inhibited the growth of the marine bacterium Ruegeria atlantica (15.2 mm at 20 μg/disk and 12.2 mm at 5 μg/disk, respectively) and 2 showed antifungal activity to Mucor hiemalis (13.8 mm at 50 μg/disk). Compounds 1-3 were cytotoxic against HL-60 (IC₅₀=0.37, 0.21, and 5.5 μM, respectively).     

Trisorbicillinone A, a novel sorbicillin trimer, from a deep sea fungus, Phialocephala sp. FL30r

A novel sorbicillin trimer, trisorbicillinone A (1), was isolated from a deep sea fungus, Phialocephala sp. FL30r. The structure and relative stereochemistry of 1 were determined based on spectroscopic methods. Trisorbicillinone A (1) showed cytotoxicity against P388 and HL60 cells with the IC₅₀ value of 9.10 and 3.14 μM, respectively.     

Guignardins A–F,spirodioxynaphthalenes from the endophytic fungus Guignardia sp. KcF8 as a new class of PTP1B and SIRT1 inhibitors

Six new guignardins A–F (1–6) were isolated from the cultures of endophytic fungus Guignardia sp. KcF8 derived of a mangrove plant Kandelia candel, along with three known analogues, palmarumycins C₁ (7), BG1 (8), and JC1 (9). Compounds 2, 3, 7, and 8 showed antimicrobial activities. Compounds 5–7 exhibited significant cytotoxicities against 10 human tumor cell lines. Compound 3 also displayed significant inhibitory activity against human protein tyrosine phosphatase 1B and histone deacetylase silent information regulator T1enzymes, two key targets for the treatment of diabetes. This is the first report on the anti-PTP1B and anti-SIRT1 activities of spirodioxynaphthalenes.     

Iriomoteolide-13a,a cytotoxic 22-membered macrolide from a marine dinoflagellate Amphidinium species

Iriomoteolide-13a (1) has been isolated from a benthic dinoflagellate Amphidinium sp. (strain KCA09053) as a new 22-membered macrolide containing one hexahydrofuro[3,2-b]furan ring, one tetrahydropyran ring, two tetrahydrofuran rings, three one-carbon branches, and three hydroxyl groups including two hemiketals. The structure of 1 was assigned on the basis of a detailed 2D NMR analysis. Compound 1 exhibited cytotoxic activity against human cervix adenocarcinoma HeLa cells (IC₅₀: 0.5 μg/mL).     

Bioactive polyketides from the fungus Astrocystis sp. BCC 22166

Five new compounds, phthalide 1, dihydroisocoumarin 2, and 3, pyrone 4, and benzophenone 5, together with nine known compounds, 3,4-dihydro-4,5,8-trihydroxy-3-methylisocoumarin, sclerotinin A, methyl-8-hydroxy-6-methylxanthone-1-carboxylate, sydowinin A, conioxanthone A, 1,3,8-trihydroxy-6-methylxanthone, 1,8-dihydroxy-3-methoxy-6-methylxanthone, coniochaetone B, and xylaranol B, were isolated from the fungus Astrocystis sp. BCC 22166. Structures of these compounds were elucidated using NMR spectroscopic and MS spectrometric analyses. Compound 1 exhibited antibacterial activity against Bacillus cereus (IC₅₀=12.5 μg/mL) while compound 2 showed cytotoxicity to KB and Vero cells (IC₅₀=22.6 and 48.2 μg/mL).     

Marine bacterial inhibitors from the sponge-derived fungus Aspergillus sp.

Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium, yielded a new tryptophan derived alkaloid, 3-((1-hydroxy-3-(2-methylbut-3-en-2-yl)-2-oxoindolin-3-yl)methyl)-1-methyl-3,4-dihydrobenzo[e][1,4]diazepine-2,5-dione (1), and a new meroterpenoid, austalide R (2), together with three known compounds (3–5). The structures of the new compounds were unambiguously elucidated on the basis of extensive one and two-dimensional NMR (¹H, ¹³C, COSY, HMBC, and ROESY) and mass spectral analysis. Interestingly, the compounds exhibited antibacterial activity when tested against a panel of marine bacteria, with 1 selectively inhibiting Vibrio species and 2 showing a broad spectrum of activity. In contrast, no significant activity was observed against terrestrial bacterial strains and the murine cancer cell line L5178Y.     

Antimalarial 20-membered macrolides from Streptomyces sp. BCC33756

Two new natural products, samroiyotmycins A (1) and B (2), along with two naturally new novclobiocin 101 (3) and 4-hydroxy-3-(3-methylbut-2-enyl)benzamide (5), and five known substances including neoantimycin, clorobiocin (4), 29-O-methylabierixin, daidzein, and 1-(3-indolyl)-2,3-dihydroxypropan-1-one have been isolated from Streptomyces sp. BCC33756. Their chemical structures were determined based on NMR spectral information and the relative stereochemistry of compound 1 was determined by X-ray crystallographic data. Both samroiyotmycins A and B exhibited antimalarial activity against Plasmodium falciparum K1—multi-drug resistant strain, with IC₅₀ values of 3.65 and 3.16 μg/mL, respectively. Compound 1 was inactive against both cancerous (MCF-7, KB) and non-cancerous (Vero) cells, while compound 2 displayed cytotoxicity against Vero cell with IC₅₀ value of 29.57 μg/mL.