Coruscol A, a new metabolite from the marine-derived fungus penicillium species

A new metabolite possessing a 1,3-dioxane ring, coruscol A (1), was isolated from the mycelium of the fungus Penicillium sp., which was separated from the Okinawan marine bivalve Mytilus coruscus, and the structure was elucidated by spectroscopic data.     

Trichodermamides A and B,cytotoxic modified dipeptides from the marine-derived fungus Trichoderma virens

Trichodermamides A (1) and B (2), two modified dipeptides, have been isolated from cultures of the marine-derived fungus Trichoderma virens. The trichodermamides possess a rare cyclic O-alkyl-oxime functionality incorporated into a six-membered ring. The structure of trichodermamide B was established by X-ray diffraction analysis, while the structure assignment of trichodermamide A, and determination of the absolute stereochemistry, was accomplished by spectral and chemical methods. Trichodermamide B displayed significant in vitro cytotoxicity against HCT-116 human colon carcinoma with an IC(50) of 0.32 microg/mL.     

Parasitenone,a new epoxycyclohexenone related to gabosine from the marine-derived fungus Aspergillus parasiticus

Bioassay-guided fractionation of an organic extract of the broth from the marine-derived fungus culture of Aspergillus parasiticus led to the isolation and subsequent structural elucidation of a new gabosine derivative, parasitenone (1), and two known benzyl alcohols, 3-chloro-4,5-dihydroxybenzyl alcohol (2) and gentisyl alcohol (3). The benzyl alcohols (2, 3) were identified as the principal free radical scavenging components. Parasitenone (1) also showed moderate activity in the free radical scavenging assay.     

Scalusamides A-C, new pyrrolidine alkaloids from the marine-derived fungus Penicillium citrinum

Three new pyrrolidine alkaloids, scalusamides A-C (1-3), were isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from the gastrointestine of a marine fish, and the structures were elucidated by spectroscopic data. The absolute stereochemistry of C-2 in the pyrrolidine unit was determined by HPLC analysis of a Marfey's derivative of the hydrolysate of 1, while that of 2 and 3 was assigned by comparison of spectroscopic data of 3 and reductive products of 1 and 2. On the other hand, each of 1-3 was found to be a mixture of epimers at C-7. Scalusamide A (1) exhibited antifungal and antibacterial activities.     

Modiolides A and B,two new 10-membered macrolides from a marine-derived fungus

Two new 10-membered macrolides, modiolides A (1) and B (2), and a new linear pentaketide, modiolin (3), were isolated from the cultured broth of a fungus Paraphaeosphaeria sp. (N-119), which was separated from a marine horse mussel, and the structures were elucidated by spectroscopic data.     

Cyclic heptapeptides, cordyheptapeptides C-E, from the marine-derived fungus Acremonium persicinum SCSIO 115 and their cytotoxic activities

Three new cycloheptapeptides, cordyheptapeptides C-E (1-3), were isolated from the fermentation extract of the marine-derived fungus Acremonium persicinum SCSIO 115. Their planar structures were elucidated on the basis of extensive MS, as well as 1D and 2D (COSY, HMQC, and HMBC) NMR spectroscopic data analyses. The absolute configurations of the amino acid residues were determined by single-crystal X-ray diffraction, Marfey's method, and chiral-phase HPLC analysis. Compounds 1 and 3 displayed cytotoxicity against SF-268, MCF-7, and NCI-H460 tumor cell lines with IC(50) values ranging from 2.5 to 12.1 μM.     

Gliotoxin analogues from a marine-derived fungus, Penicillium sp., and their cytotoxic and histone methyltransferase inhibitory activities

Seven gliotoxin-related compounds were isolated from the fungus Penicillium sp. strain JMF034, obtained from deep sea sediments of Suruga Bay, Japan. These included two new metabolites, bis(dethio)-10a-methylthio-3a-deoxy-3,3a-didehydrogliotoxin (1) and 6-deoxy-5a,6-didehydrogliotoxin (2), and five known metabolites (3-7). The structures of the new compounds were elucidated by analysis of spectroscopic data and the application of the modified Mosher's analysis. All of the compounds exhibited cytotoxic activity, whereas compounds containing a disulfide bond showed potent inhibitory activity against histone methyltransferase (HMT) G9a. None of them inhibited HMT SET7/9.     

Asperaculin A, a sesquiterpenoid from a marine-derived fungus, Aspergillus aculeatus

A novel sesquiterpenoid, asperaculin A, possessing a novel [5,5,5,6]fenestrane ring system, was isolated from the marine-derived fungus Aspergillus aculeatus CRI323-04. The structure of asperaculin A was established by analysis of spectroscopic data. The name aspergillane is proposed for the sesquiterpene skeleton in asperaculin A.     

Cytotoxic polyketides from a marine-derived fungus Aspergillus glaucus

Eight new aromatic polyketides (2, 4-6, 8, 14, 16, and 17) together with eight known analogues (3, 7, 9-13, and 15) were isolated from the marine-derived fungus Aspergillus glaucus. The structures and stereochemistry of the new compounds were elucidated by spectroscopic and chemical methods, and their cytotoxicities were evaluated against the HL-60 and A-549 cell lines.     

Cladionol A, a polyketide glycoside from marine-derived fungus Gliocladium species

A new polyketide glycoside, cladionol A (1), was isolated from the cultured broth of a fungus Gliocladium sp., which was separated from sea grass Syringodium isoetifolium, and the structure was elucidated by spectroscopic data. The relative stereochemistry of C-2-C-3 was assigned by mainly J-based configuration analysis, while those of two sugar units were elucidated to be beta-mannopyranoside and arabitol on the basis of NOESY data and/or 1H-1H couplings. Furthermore, the absolute configuration of the mannose moiety was determined as the D-form on the basis of chiral HPLC analysis of a benzoyl derivative of the acid hydrolysate of 1. Cladionol A (1) exhibited modest cytotoxicity.     

Ten-membered lactones from the marine-derived fungus Curvularia sp

Investigation of the secondary metabolites of the marine-derived fungus Curvularia sp. yielded four new 10-membered lactones (1-4), along with the known modiolide A (5). The structures of 1-4 were characterized on the basis of spectroscopic and MS data and resemble known 10-membered lactones, but feature modified oxidation patterns around their macrocycles.     

Bioactive metabolites from a marine-derived strain of the fungus Emericella variecolor

From a marine-derived strain of the fungus Emericella variecolor, varitriol (1), varioxirane (2), dihydroterrein (3), and varixanthone (4), besides the known mold metabolites ergosterol, terrein, shamixanthone, and tajixanthone hydrate, were identified. The chemical structures of 1-4 were established by means of spectroscopic techniques and some chemical transformations. In the NCI's 60-cell panel, varitriol (1) displayed increased potency toward selected renal, CNS, and breast cancer cell lines. Varixanthone (4) showed antimicrobial activity.     

Lucentamycins A-D, cytotoxic peptides from the marine-derived actinomycete Nocardiopsis lucentensis

Four new 3-methyl-4-ethylideneproline-containing peptides, lucentamycins A-D (1-4), have been isolated from the fermentation broth of a marine-derived actinomycete identified by phylogenetic methods as Nocardiopsis lucentensis (strain CNR-712). The planar structures of the new compounds were assigned on the basis of 1D and 2D NMR spectroscopic techniques, while the absolute configurations of the amino acid residues were determined by application of the advanced Marfey method. Lucentamycins A (1) and B (2) showed significant in vitro cytotoxicity against HCT-116 human colon carcinoma.     

Arugosins G and H: prenylated polyketides from the marine-derived fungus Emericellanidulans var. acristata

The fungus Emericella nidulans var. acristata was isolated as an endophyte from a Mediterranean green alga. Cultivation of this fungus yielded two new compounds, arugosins G (1) and H (2), together with the known metabolites 3-9. Arugosins (1-4) are benzophenone derivatives, biosynthetically related to the xanthones 5, 6, and 9. The indole alkaloid 7 displayed antitumor activity in a panel of 36 human tumor cell lines, exhibiting a mean IC(50) value of 5.5 microg/mL in an in vitro survival and proliferation assay. Furthermore, compounds 3 and 4 showed moderate antitumor activity toward individual tumor cell lines. None of compounds 1-8 exhibited any immunostimulatory activity assessed as the capacity to induce cytokines in PBMCs from healthy donors.     

Pentaketides relating to aspinonene and dihydroaspyrone from a marine-derived fungus, Aspergillus ostianus

Three new pentaketides, aspinotriols A ( 1) and B ( 3) and aspinonediol ( 5), were isolated together with two known compounds, aspinonene ( 7) and dihydroaspyrone ( 9), from the marine fungus Aspergillus ostianus strain 01F313, which was collected in Pohnpei and cultured with bromine-modified artificial seawater. The structures of the new compounds were determined by spectroscopic analyses including 1D and 2D NMR. Although 1 and 3 are diastereomers, they show nearly superimposable (1)H and (13)C NMR spectra. The absolute configurations of compounds 1, 3, 5, and 9 were elucidated by the modified Mosher's method.     

Isolation and structure assignments of rostratins A-D, cytotoxic disulfides produced by the marine-derived fungus Exserohilum rostratum

Four new cytotoxic disulfides, rostratins A-D (1-4), were isolated from the whole broth of the marine-derived fungus Exserohilum rostratum (Drechsler), a fungal strain found associated with a marine cyanobacterial mat. The structures of these cyclic dipeptides were established through chemical degradation and a variety of two-dimensional NMR techniques. The absolute configurations of the rostratins were determined by the modified Mosher method. In the case of the polyhydroxylated compound 1 and the mercaptol 4, regioselective acylation was achieved by modulating the reaction temperature while monitoring the progress of the reaction by 1H NMR. Rostratins A, B, C, and D showed in vitro cytotoxicity against human colon carcinoma (HCT-116) with IC50 values of 8.5, 1.9, 0.76, and 16.5 microg/mL, respectively.     

Novel open-chain cytochalsins from the marine-derived fungus Spicaria elegans

Six novel open-chain cytochalasins (1-6) and one known [12]-cytochalasin (7) have been isolated from the fermentation broth of a marine-derived fungus, Spicaria elegans. Cytochalasins Z10-Z15 (1-6) are the first reported cytochalasins that contain an open chain to date. The structures of these new compounds were elucidated by spectroscopic methods. The cytotoxic effects on P388, A-549, HL-60, and BEL-7402 cell lines of all compounds were evaluated by the MTT method.     

Diastereomeric quinolinone alkaloids from the marine-derived fungus Penicillium janczewskii

From Penicillium janczewskii, obtained from a marine sample, two new diastereomeric quinolinones, 3S,4R-dihydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (1) and 3R,4R-dihydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (2), were identified, along with two known alkaloids, peniprequinolone (3) and 3-methoxy-4-hydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (4). Cytotoxicity testing on eight tumor cell lines revealed a moderate specificity of 2 on SKOV-3 cells.     

Gentisyl alcohol derivatives from the marine-derived fungus Penicillium terrestre

Nine new gentisyl alcohol derivatives, namely, the trimeric terrestrol A (8), dimeric terrestrols B-H (1-7), and a monomeric derivative (12), together with four known analogues (9-11, 13) were isolated from the marine-derived fungus Penicillium terrestre. The structures of the new compounds were elucidated by spectroscopic methods including one- and two-dimensional NMR as well as low- and high-resolution mass spectrometric analysis. These new compounds (1-8, 12) showed cytotoxic effects on HL-60, MOLT-4, BEL-7402, and A-549 cell lines with IC50 values in the range 5-65 microM. Compound 6 also showed moderate inhibitory activity against protein tyrosine kinases (Src and KDR). Furthermore, all new compounds exhibited moderate radical scavenging activity against DPPH with IC50 values in the range 2.6-8.5 microM.     

HLE-inhibitory alkaloids with a polyketide skeleton from the marine-derived fungus Coniothyrium cereale

The marine endophytic fungus Coniothyrium cereale produces the structurally unusual polyketide-type alkaloids (-)-cereolactam (1) and (-)-cereoaldomine (3), incorporating a lactam and an imine functionality, respectively, as well as the related metabolite (-)-trypethelone (2). Compounds 1 and 3 showed selective inhibition of human leukocyte elastase with IC50 values of 9.28 and 3.01 μM, respectively. Compound 2 was found to be inhibitory toward Mycobacterium phlei, Staphylococcus aureus, and Escherichia coli and also cytotoxic against mouse fibroblast cells (IC50=7.5 μM).