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.     

Amphirionin-5, a novel linear polyketide from a cultured marine dinoflagellate Amphidinium species with a potent cell proliferation-promoting activity

A novel linear polyketide, amphirionin-5 (1), has been isolated from the cultivated algal cells of the benthic dinoflagellate Amphidinium sp. (strain KCA09053), and the structure was elucidated on the basis of detailed analyses of 1D and 2D NMR data. Amphirionin-5 (1) resulted in a 282% increase in the proliferation of murine bone-marrow derived stromal ST-2 cells and 320% increase in the proliferation of murine osteoblastic MC3T3-E1 cells.     

Malbrancheamide, a new calmodulin inhibitor from the fungus Malbranchea aurantiaca

Bioassay-directed fractionation of an ethyl acetate extract (mycelia and broth) of the fungus Malbranchea aurantiaca led to the isolation of the novel phytotoxic alkaloid (5aS,12aS,13aS)-8,9-dichloro-12,12-dimethyl-2,3,11,12,12a,13-hexahydro-1H,6H-5a,13a (epiminomethano)indolizino[7,6b]carbazol-14-one (1) of the brevianamide series. The phytotoxin was given the trivial name of malbrancheamide (1). The structure of 1 was unequivocally established by UV, NMR, MS and X-ray studies. The absolute configuration was established by X-ray analysis according to the method of Flack. According to the conformational studies using molecular mechanics analyses, 1 exists in one preferred conformation, which was optimized by DFT calculations. Compound 1 caused moderate inhibition of radicle growth of Amaranthus hypochondriacus (IC₅₀=0.37 μM) and inhibited the activation of the calmodulin-dependent enzyme PDE1 (IC₅₀=3.65±0.74 μM). This effect was comparable to that of chlorpromazine (IC₅₀=2.75±0.87 μM) a well characterized CaM antagonist. The inhibition mechanism of 1 was competitive with respect to CaM according to a kinetic analysis.     

Hericirine,a novel anti-inflammatory alkaloid from Hericium erinaceum

A novel ergosterol conjunction-type alkaloid, hericirine (1), was isolated from the dried fruiting bodies of Hericium erinaceum. The overall framework of 1 was isolated, and combined with hericerin and ergosterol. Its structure was elucidated based on spectroscopic analysis using 1D and 2D NMR, IR and HRESIMS techniques. We found that hericirine significantly inhibited protein expression of iNOS and COX-2 and reduced NO, PGE₂, TNF-α, IL-6 and IL-1β production in RAW264.7 cells exposed to LPS.     

ZHD-0501, a novel naturally occurring staurosporine analog from Actinomadura sp. 007

ZHD-0501, a novel naturally occurring staurosporine analog showing anticancer activity in vitro, was isolated from the fermentation broth of a marine-derived Actinomadura sp. 007 through a bioassay-guided separation procedure and its structure elucidated by spectroscopic methods. ZHD-0501 provided the first example of staurosporin analog carrying a heterocycle fused to the pyran ring adopting a boat conformation with C-2′ and C-5′ as the bow and stern, which inhibited the proliferation of mammalian cancer A549, BEL-7402, HL60, P388, and tsFT210 cells.     

Holophyllin A,a rearranged abietane-type diterpenoid from the trunk of Abies holophylla

Holophyllin A (1), a novel rearranged abietane-type diterpenoid was isolated, together with a new diterpene glycoside, holophyllin B (2), from the trunk of Abies holophylla. The structures of 1 and 2 were established by extensive spectroscopic analyses and their absolute configurations were determined by ECD calculation. All the isolates were tested for their inhibitory effects on NO production in LPS-activated murine microglial cells.     

Orirubenones A, B and C, novel hyaluronan-degradation inhibitors from the mushroom Tricholoma orirubens

Three new compounds, orirubenone A (1), B (2) and C (3) were isolated from the mushroom Tricholoma orirubens. Their structures were determined by spectral analyses. These compounds inhibited hyaluronan-degradation by human skin fibroblasts.     

Suffruticosine, a novel octacyclic alkaloid with an unprecedented skeleton from Securinegasuffruticosa (Pall.) Rehd.

A novel securinega alkaloid, suffruticosine (1), was isolated from the leaves and barks of Securinegasuffruticosa. The structure of 1, characterized by a fused complex octacyclic system, was elucidated by combined spectroscopic techniques, especially 2D NMR and CD spectral analyses.     

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.     

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.     

Synthesis of the first unnatural schisantherins and their effects in multidrug-resistant cancer cells

Schisandrol A, a dibenzocyclooctadiene lignan, was obtained by a simplified procedure from Schisandra chinensis fruits. Its reaction with carboxylic acids to give new esters (schisantherins) required special conditions such as microwave irradiation. An X-ray single crystal structure analysis of schisandrol A revealed a sterical shielding of the secondary OH group as the likely reason. The cinnamoate inhibited the P-gp drug transporters of multidrug-resistant human Kb-V1 cervix carcinoma cells better than the natural benzoate and comparable to the clinical sensitizer verapamil.     

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.     

Aspergiolide A, a novel anthraquinone derivative with naphtho[1,2,3-de]chromene-2,7-dione skeleton isolated from a marine-derived fungus Aspergillus glaucus

Aspergiolide A (1), an anthraquinone derivative with naphtho[1,2,3-de]chromene-2,7-dione skeleton, has been isolated from cultures of a marine-derived fungus Aspergillus glaucus. The structure and stereochemistry of 1 was determined by NMR and X-ray diffraction analyses. Compound 1 showed selective cytotoxicities against A-549, HL-60, BEL-7402, and P388 cell lines.     

Sanctolide A, a 14-membered PK-NRP hybrid macrolide from the cultured cyanobacterium Oscillatoria sancta (SAG 74.79)

Sanctolide A (1), a 14-membered polyketide-nonribosomal peptide (PK-NRP) hybrid macrolide, was isolated from the cultured cyanobacterium Oscillatoria sancta (SAG 74.79). The planar structure was determined using various spectroscopic techniques including HRESIMS, and 1D and 2D NMR analyses. The relative configuration was assigned by J-based configurational analysis in combination with NOE correlations. The absolute configuration was determined by Mosher ester and enantioselective HPLC analyses. The structure of sanctolide A (1) features a rare N-methyl enamide and a 2-hydroxyisovaleric acid, which are incorporated to form a 14-membered macrolide ring structure, comprising a new type of cyanobacterial macrolides derived from a PKS-NRPS hybrid biosynthetic pathway.     

Sinutriangulin A, a novel diterpenoid from the soft coral Sinularia triangula

A novel compound, named sinutriangulin A (1), was isolated from the soft coral Sinularia triangula. The compound possesses a new carbon skeleton that is derived from the cubitane skeleton. The structure was determined by extensive spectroscopic analyses. In addition, compound 1 exhibited weak cytotoxicity toward human tumor cell lines CCRF-CEM and DLD-1.     

Coibanoles, a new class of meroterpenoids produced by Pycnoporus sanguineus

Three new terpenoids of mixed biosynthetic origin were isolated from the culture filtrate of the endophytic fungus Pycnoporus sanguineus. Their structures were determined by extensive spectroscopic analyses. We have named these tricyclic and tetracyclic metabolites ‘coibanoles A-C’ in reference to Coiba Island and Coiba National Park, Panamá, from which the plant and endophyte were collected. The extract was inactive to the human parasites Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum at a test concentration of 10 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.     

Daphniglaucin C, a novel tetracyclic alkaloid from Daphniphyllum glaucescens

A novel Daphniphyllum alkaloid with an unprecedented tetracyclic ring system consisting of an octahydroindole and a hexahydroazulene rings, daphniglaucin C (1), has been isolated from the leaves of Daphniphyllum glaucescens and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data. Daphniglaucin C (1) inhibited the polymerization of tubulin.     

Shimalactone A, a novel polyketide, from marine-derived fungus Emericella variecolor GF10

Shimalactone A (1), a novel polyketide having bicyclo[4.2.0]octadiene and oxabicyclo[2.2.1]heptane units, was isolated from a cultured marine fungus of Emericella variecolor GF10. The stereo structure of 1 was deduced from 2D NMR and X-ray crystallographic analyses of 1 and its derivatives. The absolute structure of 1 was determined by application of the CD allylic benzoate rule to the benzoate derivative of 1. Shimalactone A (1) induced neuritogenesis at 10 μg/mL against neuroblastoma Neuro 2A cells.     

Bisbakuchiols A and B, novel dimeric meroterpenoids from Psoralea corylifolia

Two novel dimeric meroterpenoids, bisbakuchiols A and B, along with (S)-bakuchiol were isolated from the seeds of Psoralea corylifolia L. (Fabaceae). Bisbakuchiols A and B contain an unprecedented dimeric meroterpenoid skeleton in which two meroterpenes are linked through a dioxane bridge. All compounds were evaluated for their potential to inhibit hypoxia-inducible factor-1 (HIF-1) activation induced by hypoxia in a HIF-1-mediated reporter gene assay in AGS human gastric cancer cells. (S)-Bakuchiol inhibited hypoxic activation of HIF-1 with an IC₅₀ value of 6.1 μM.