Chaetomugilins I-O, new potent cytotoxic metabolites from a marine-fish-derived Chaetomium species. Stereochemistry and biological activities

Chaetomugilins I-O were isolated from a strain of Chaetomium globosum originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, as well as chemical transformations. These compounds exhibited significant growth inhibition of cultured P388, HL-60, L1210, and KB cell lines. In addition, chaetomugilin I showed selective cytotoxic activity against 39 human cancer cell lines.     

Cephalimysin A, a potent cytotoxic metabolite from an Aspergillus species separated from a marine fish

Cephalimysin A (1) was isolated from a strain of Aspergillus fumigatus originally separated from the marine fish Mugil cephalus, and its absolute stereostructure was elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformations including the modified Mosher’s method. This compound exhibited significant cytotoxicity against cultured P388 cells and HL-60 cells.     

Halichoblelides B and C,potent cytotoxic macrolides from a Streptomyces species separated from a marine fish

Halichoblelide B (1) and C (2), novel macrolides with potent cytotoxicity against tumor cells in culture, have been isolated from a strain of Streptomyces hygroscopicus originally derived from the marine fish Halichoeres bleekeri, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and chemical transformations. These compounds exhibited significant cytotoxicity against human cancer cell lines.     

Absolute stereostructures of inoterpenes A-F from sclerotia of Inonotus obliquus

Six new lanostane-type triterpenes, inoterpenes A (1), B (2), C (3), D (4), E (5), and F (6), were isolated from the sclerotia of Inonotus obliquus together with six known constituents. The chemical structures of new triterpenes 1-6 were characterized on the basis of chemical and physicochemical evidence including the application of the modified Mosher's method.     

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).     

Sorbifuranones A-C, sorbicillinoid metabolites from Penicillium strains isolated from Mediterranean sponges

Three novel natural products, sorbifuranones A-C (4-6), were isolated from a Penicillium chrysogenum fungus isolated from the marine sponge Ircinia fasciculata. Sorbifuranones B (5) and C (6) and 2′,3′-dihydrosorbicillin, a putative precursor to sorbifuranone B, were also found in the culture of another Penicillium strain, which was isolated from the sponge Tethya aurantium. Their constitutions were elucidated mainly by 2D NMR. NOE correlations in combination with quantum chemical calculations and comparison of experimental and calculated electronic circular dichroism (CD) spectra permitted assignment of the absolute configuration of sorbifuranone C. The structures hint at a two-step cleavage-cyclization sequence of sorbifuranone A (4) leading to the spiro compound sorbifuranone C, while sorbifuranone B is likely to be the respective cleavage product of a putative 2′,3′-dihydrosorbifuranone A, which cannot cyclize further.     

Chaetominedione, a new tyrosine kinase inhibitor isolated from the algicolous marine fungus Chaetomium sp.

A marine fungal isolate, identified as Chaetomium sp., was cultivated and found to produce a novel benzonaphthyridinedione derivative, chaetominedione (1). In addition to the known fungal metabolites, 2-furancarboxylic acid (2) and 5-(hydroxymethyl)-2-furancarboxylic acid (3) were obtained. The structures of all the compounds were determined based on extensive spectroscopic measurements (1D and 2D NMR, MS, UV, and IR). The total extract and compound 1 had significant inhibitory activity toward p56^lck tyrosine kinase (18.7% and 93.6% enzyme inhibition at 200 μg/mL, respectively).     

Absolute stereostructures of halenaquinol and halenaquinol sulfate,pentacyclic hydroquinones from the okinawan marine sponge xestospongia sapra, as determined by theoretical calculation of CD spectra

The absolute stereostructures of two pentacyclic hydroquinones, halenaguinol ($\text{1}$) and halenaquinol sulfate ($\text{2}$) from the Okinawan marine sponge Xestospongia sapra, have been determined by means of theoretical calculation of CD spectra.     

Kehokorins A-C, novel cytotoxic dibenzofurans isolated from the myxomycete Trichia favoginea var. persimilis

Kehokorins A (1)-C (3), three novel dibenzofurans, have been isolated from field-collected fruit bodies of the myxomycete, Trichia favoginea var. persimilis, and their structures were elucidated by spectral data. Kehokorin A (1) was a α-l-rhamnopyranoside of kehokorin B (2), while kehokorin C (3) was a 1-demethoxy analog of 2. Kehokorin A (1) was cytotoxic against HeLa cells with an IC₅₀ value of 1.5 μg/mL.     

Myriastramides A-C, new modified cyclic peptides from the Philippines marine sponge Myriastra clavosa

Chemical investigation of the Philippines marine sponge Myriastra clavosa has resulted in the isolation of three new cyclic octapeptides, myriastramides A (1), B (2), and C (3). The structures of compounds 1-3 were assigned based on extensive NMR spectroscopic analyses and a series of degradation and derivatization studies.     

Musanahol: a new aureonitol-related metabolite from a Chaetomium sp.

Two antibacterial furano-polyenes, (−)-musanahol (1) and 3-epi-aureonitol (5), and a fatty acid, linoleic acid (8) were isolated from the laboratory cultures of a Chaetomium sp. accessed from tomato fruits, and grown on YMG medium (yeast extract, glucose, malt extract and water) at pH 5.8-6.0. The structure of compound 1, a new furano-polyene, was elucidated by spectroscopic methods that include extensive 2D NMR experiments, double resonance experiments, Mosher's method and PM3 calculations. (−)-Musanahol (1) and 3-epi-aureonitol (5) were present in the culture filtrate of the fungus. 3-epi-Aureonitol (5) completely inhibited the growth of Streptococcus pyogenes at 15.63 μg/mL and Escherichia coli, Staphylococcus aureus, Salmonella choleraesuis and Corynebacterium diphtheriae at 31.25 μg/mL, whereas (−)-musanahol (1) lacked the antimicrobial potency of compound 5 in spite of the similarities in their structures. Linoleic acid (8) was isolated from the mycelia of the fungus; it inhibited the growth of S. aureus and Bacillus subtilis at a minimum concentration of 15.62 μg/mL.     

Absolute configuration of scopadulane diterpenes from Calceolaria species

The absolute configuration of the diterpenoid 13-acetoxyscopadulane, also known as demalonyl thyrsiflorin A acetate (5), isolated from several Calceolaria species has been established by vibrational circular dichroism spectroscopy in combination with density functional theory calculations, as well as by evaluation of Flack and Hooft single crystal X-ray parameters. It follows 5 belongs to the normal enantiomeric series of diterpenes, and that at least 11 out of 13 scopadulanes, for which chemical and biogenetical relationships with 5 are established, also belong to the same stereochemical series.     

Syntheses of two cytotoxic polyunsaturated pyrrole metabolites of the marine sponge Mycale micracanthoxea

Starting from eicosapentaenoic acid (EPA) the marine, naturally occurring, pyrrole derivatives, mycalazol 5 and mycalazal 2 have been synthesized. The Stille coupling reaction is a key step in the syntheses.     

Feroniellins A-C, novel cytotoxic furanocoumarins with highly oxygenated C10 moieties from Feroniella lucida

Three new furanocoumarins, named feroniellins A (1), B (2), and C (3), were isolated from the roots of Feroniella lucida. Compounds 1-3 are novel structures having an oxolane, oxane, and oxepane moiety. Their overall structures and configurations were determined by spectral and chemical methods. The cytotoxicities of 1-3 were evaluated against human KB and HeLa carcinoma 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.     

Tandyukisin,a novel ketoaldehyde decalin derivative,produced by a marine sponge-derived Trichoderma harzianum

Tandyukisin (1), a novel decalin derivative with an enolic β-ketoaldehyde, has been isolated from a strain of Trichoderma harzianum OUPS-111D-4 originally derived from the marine sponge Halichondria okadai, and its structure has been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques. In addition, the absolute configuration for 1 was established by the application of CD spectrum to the tribenzoate derivative. This compounds exhibited moderate cytotoxicity against human cancer 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.     

Acremines H-N, novel prenylated polyketide metabolites produced by a strain of Acremonium byssoides

Five novel metabolites, acremines H-N, have been isolated from malt extract-peptone-glucose agar cultures of a strain of Acremonium byssoides. Their structures and stereochemistry were elucidated using a combination of ¹³C and ¹H homo and heteronuclear 2D NMR experiments. Acremines H-N inhibited the germination of sporangia of Plasmopara viticola.     

Aspercyclide A-C, three novel fungal metabolites from Aspergillus sp. as inhibitors of high-affinity IgE receptor

Immunoglobin E (IgE) binds to the high-affinity IgE receptor on mast cells and basofils and causes release of inflammatory compounds that leads to allergic diseases. Inhibition of the ligand binding could lead to blockade of the release of inflammation causing compounds and thus alleviate asthma and other allergic diseases. Natural product screening and bioassay-guided isolation of an extract of Aspergillus sp. led to the identification of three novel 11-membered macrocyclic biphenyl ether lactones, aspercyclides A-C. Aspercyclide A inhibited the IgE binding with an IC₅₀ of 200 μM. The isolation, structure elucidation, absolute stereochemistry, and the binding activities of these compounds are described.     

Takaneones A-C, prenylated butylphloroglucinol derivatives from Hypericum sikokumontanum

Three new prenylated butylphloroglucinol derivatives, takaneones A-C (1-3), were isolated from the MeOH extracts of the aerial parts of Hypericum sikokumontanum together with two new prenylated phloroglucinol derivatives, takaneols A and B (4 and 5). The structures of the isolated compounds were elucidated by exhaustive spectroscopic analysis. The cytotoxicities of the isolated compounds against human cancer cell lines were evaluated. Compounds 2-4 showed cytotoxicities against K562/Adr multi-drug resistant (MDR) cancer cells with IC₅₀ values ranging from 4.7 to 10.0 μg/mL, which were slightly more potent than doxorubicin. Their potency of cytotoxicities against MDR cancer cell lines (KB-C2 and K562/Adr) were similar to those against sensitive cell lines (KB and K562).