Polyketides from the marine-derived fungus Ascochyta salicorniae and their potential to inhibit protein phosphatases

Chemical investigation of the marine fungus Ascochyta salicorniae led to the isolation of two new epimeric compounds, ascolactones A (1) and B (2), in addition to the structurally-related polyketides hyalopyrone (3), ascochitine (4), ascochital (5) and ascosalipyrone (6). The absolute configurations of the epimeric compounds 1 and 2 were assigned as (1R,9R) and (1S,9R), respectively, through simulation of the chiroptical properties using quantum-chemical CD calculations, and chiral GC-MS subsequent to oxidative cleavage (Baeyer-Villiger oxidation) of the side chain. In silico screening using the PASS software identified some of the A. salicorniae compounds (1-6) as potential inhibitors of protein phosphatases. Compound was found to inhibit the enzymatic activity of MPtpB with an IC(50) value of 11.5 microM.     

Ascosalipyrrolidinone A, an antimicrobial alkaloid, from the obligate marine fungus Ascochyta salicorniae

From the green alga Ulva sp., the endophytic and obligate marine fungus Ascochyta salicorniae was isolated. A. salicorniae was mass cultivated and found to produce the unprecedented and structurally unusual tetramic acid containing metabolites ascosalipyrrolidinones A (1) and B (2). Additionally, the new natural product ascosalipyrone (3) and the known metabolites 4 and 5 were obtained. Ascosalipyrrolidinone A (1) has antiplasmodial activity toward Plasmodium falciparum strains K1 and NF 54, as well as showing antimicrobial activity and inhibiting tyrosine kinase p56lck.     

Flavusides A and B, antibacterial cerebrosides from the marine-derived fungus Aspergillus flavus

Flavusides A (1) and B (2), two new antibacterial cerebroside derivatives, and the previously described phomaligol A (3), kojic acid (4), methyl kojic acid (5), and dimethyl kojic acid (6) have been isolated from the extract of a marine isolate of the fungus Aspergillus flavus. The structure and absolute stereochemistry of two cerebrosides were assigned on the basis of NMR and Tandem FAB-MS/MS experiments. Compounds 1, 2, and 3 exhibited a mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The minimum inhibitory concentration (MIC) values for each strain are as follows: compounds 1 and 2 showed 15.6 μg/ml for S. aureus and 31.2 μg/ml for methicillin-resistant S. aureus and multidrug-resistant S. aureus, and compound 3 exhibited 31.2 μg/ml for S. aureus and methicillin-resistant S. aureus and 62.5 μg/ml for multidrug-resistant S. aureus.     

Perpyrrospirone A,an unprecedented hirsutellone peroxide from the marine-derived Penicillium citrinum

Perpyrrospirone A (1) characterized an unprecedented 6/5/6/8/5/13/6 oxahexacyclic scaffold with a unique peroxide-bridged 8,9-dioxa-2-azaspiro[4.7]dodecane core from marine-derived Penicillium citrinum. Compounds 2 and 3 possessed rare oxatetracyclic (6/5/6/5) skeleton fused with a 13-menbered-ring macrocyclic moiety. Their structure and absolute configurations were determined by comprehensive spectroscopic analyses, ECD data coupled with TD-DFT calculations and X-ray diffraction experiments. In addition, 7 showed cytotoxicity and induced apoptosis of Hela cells in a dose-dependent manner after a 48 h treatment.     

Absolute stereochemistry of citrinadins a and B from marine-derived fungus

[Structure: see text]. Citrinadin A (2) is a pentacyclic indolinone alkaloid isolated from the cultured broth of a fungus, Penicillium citrinum, which was separated from a marine red alga. The absolute stereochemistry of the pentacyclic core in 2 and its new congener, citrinadin B (1), was elucidated by analysis of the ROESY spectrum for the chlorohydrin derivative (3) of 1 as well as comparison of the electronic circular dichroism (ECD) spectra for 1 and 2 with those of known spirooxiindole alkaloids. On the other hand, the absolute configuration at C-21 bearing an epoxide ring was assigned as S by comparison of the vibrational circular dichroism (VCD) spectra of 1 with those of model compounds 2S- and 2R-2,3-epoxy-3,3-dimethyl-1-phenylpropan-1-one (4a and 4b, respectively).     

Myrothenones A and B, cyclopentenone derivatives with tyrosinase inhibitory activity from the marine-derived fungus Myrothecium sp

New 3-amino-5-ethenylcyclopentenones, myrothenones A (4) and B (5), were isolated together with known 6-n-pentyl-alpha-pyrone (1), trichodenone A (2), and cyclonerodiol (3) from the marine algicolous fungus of genus of Myrothecium. The structure and absolute stereochemistry of the new compounds were established by spectral interpretation and X-ray analysis. Compounds 1 and 4 exhibited a tyrosinase inhibitory activity with IC(50) value of 0.8 and 6.6 muM, respectively, which are more active than kojic acid (IC(50), 7.7 muM) currently being used as a functional personal-care compound.     

A new polyketide,penicillolide from the marine-derived fungus Penicillium sacculum

A new polyketide, penicillolide (1) was isolated from the fermentation broth of the marine-derived fungus Penicillium sacculum GT-308. Compound 1 is a polyketide with a unique carbon skeleton. The structure of this compound was established via extensive spectroscopic analyses including 1D-, 2D-NMR, and HRESI-MS.     

A new alkaloid from the marine-derived fungus Hypocrea virens

A new alkaloid, 2-methylimidazo[1,5-b]isoquinoline-1,3,5(2H)-trione, was isolated from the EtOAc extract of the marine-derived fungus Hypocrea virens. Its structure was confirmed by spectroscopic methods (1D and 2D NMR, MS).     

Coumarins with an unprecedented tetracyclic skeleton and coumarin dimers from chemically engineered extracts of a marine-derived fungus

The unprecedented tetracyclic coumarin derivatives 1 and 2 and the coumarin dimers 3–5 were isolated from chemically engineered extracts (coumarin dimerization of natural extract) of the marine-derived fungus Eurotium rubrum. The structures of these compounds were established using NMR, MS and IR methods. The absolute configuration of 1 was determined by ECD calculations. The unprecedented tetracyclic coumarin skeleton was generated by domino-Knoevenagel-Diels-Alder reactions. Compounds 1–5 showed tyrosinase inhibitory activity (IC₅₀?=?1.7, 1.2, 4.9, 1.8 and 2.9?μM, respectively). The isolated coumarin derivatives 1–5 were not observed by HPLC analysis in crude extracts of E. rubrum, suggesting that chemically engineered extract generated these new coumarin derivatives with tyrosinase inhibitory activity.     

Agariblazeispirols A and B, an unprecedented skeleton from the cultured mycelia of the fungus, Agaricus blazei

Agariblazeispirols A and B, which have a unique steroidal skeleton, have been isolated from the cultured mycelia of Agaricus blazei (Agaricaceae). The absolute structure of Agariblazeispirol A was established to be (20S,22R,23R,24S)-13β,22:22,25-diepoxy-5-methoxy-14β-methyl-18-nor-des-A-ergosta-5,7,9,11-tetraen-23-ol by extensive 1D and 2D NMR spectral data, and X-ray analysis. The structure of Agariblazeispirol B was elucidated to be a stereoisomer of agariblazeispirol A at its carbon 22, (20S,22S,23R,24S)-13β,22:22,25-diepoxy-5-methoxy-14β-methyl-18-nor-des-A-ergosta-5,7,9,11-tetraen-23-ol by comparison of extensive 1D and 2D NMR spectral data with those of agariblazeispirol A. Both compounds showed a moderate circumvention of drug resistance on mouse leukemia P388/VCR cells.     

Pestalustaines A and B,unprecedented sesquiterpene and coumarin derivatives from endophytic fungus Pestalotiopsis adusta

Pestalustaines A (1) and B (2), one unique sesquiterpene possessing an unusual 5/6/7-fused tricyclic ring system and one unprecedented coumarin derivative bearing 6/6/5/5-fused tetracyclic ring system, were isolated from the plant-derived Pestalotiopsis adusta. Their structures with absolute configurations were established by extensive NMR analysis, X-ray crystallography, and CD spectra associated with TD-DFT calculation. Hypothetical biosynthetic pathways for compounds 1 and 2 are proposed. Compounds 1 and 2 showed weak to moderate cytotoxic activities against three human tumor cell lines HeLa, HCT116, and A549, whose IC₅₀ values were ranged from 21.01 to 55.43?μM.     

Seragakinone A, a new pentacyclic metabolite from a marine-derived fungus

A new anthracycline-derived pentacyclic metabolite, seragakinone A (1), was isolated from the mycelium of an unidentified fungus, which was separated from the Okinawan marine rhodophyta Ceralodictyon spongiosum, and the structure was elucidated by spectroscopic data.     

Vercytochalasins A and B: Two unprecedented biosynthetically related cytochalasins from the deep-sea-sourced endozoic fungus Curvularia verruculosa

Vercytochalasins A (1) and B (2), two biosynthetically related cytochalasins featuring novel structure and substituents, were isolated from the endozoic fungus Curvularia verruculosa which was associated with the deep-sea squat lobster Shinkaia crosnieri collected from the cold seep environment in South China sea. Their structures were elucidated by detailed interpretation of NMR spectroscopic and mass spectrometric data. The absolute configurations were confirmed by NOESY experiments as well as by DP4+ and ECD calculations. Differed from common cytochalasins, compound 1 is an uncommon secocytochalasin featuring the ester group cleaved between C-9 and C-23, and incorporating an additional oxygenated C4 unit which coupled with C-20 and C-22 to form a new substituted cyclohexenone moiety, while compound 2 contains an unusual 2?hydroxy-3-oxobutan-2-yl unit at C-22. Both compounds are distinctive from the commonly described cytochalasins. Compound 1 exhibited potent activity against angiotensin-I-converting enzyme (ACE) whereas compound 2 showed antibacterial activity. Molecular docking simulations were performed to explore the intermolecular interaction of compounds 1 and 2 with ACE.     

Citrinadin A, a novel pentacyclic alkaloid from marine-derived fungus Penicillium citrinum

[structure: see text] A novel pentacyclic alkaloid, citrinadin A (1), was isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from a marine red alga, and the structure was elucidated by spectroscopic data. The relative stereochemistry of the pentacyclic core was assigned on the basis of NOESY data and (1)H-(1)H coupling constants, and the presence of an N,N-dimethyl-L-valine residue in 1 was determined by chiral HPLC analysis of the hydrolysate.     

Perinadine A, a novel tetracyclic alkaloid from marine-derived fungus Penicillium citrinum

[structure: see text] A novel tetracyclic alkaloid, perinadine A (1), was isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from the gastrointestine of a marine fish, and the structure was elucidated on the basis of spectroscopic data including 2D NMR spectra. Biogenetically, perinadine A (1) may be derived from citrinin (4), a well-known mycotoxin, and a scalusamide A-type pyrrolidine alkaloid.     

New metabolites from the marine-derived fungus Aspergillus fumigatus

A new alkaloid, fumiquinazoline K (1), and a new nordammarane triterpenoid (2), together with three known diketopiperazines (3-5) and tryptoquivaline F (6) have been isolated from a marine strain of Aspergillus fumigatus KMM 4 631 associated with the soft coral Sinularia sp. Their structures were determined by HR-MS and 1D and 2D NMR. Compounds 3-5 exhibit weak cytotoxicity against cytoplasm non-specific esterase in Ehrlich carcinoma cells. Compound 3 also induces early apoptosis of the same cells in a non-toxic range of concentrations.     

New virescenosides from the marine-derived fungus Acremonium striatisporum

Five new diterpene glycosides, virescenosides Z4-Z8 (1-5) have been isolated from a marine strain of Acremonium striatisporum KMM 4401 associated with the holothurian Eupentacta fraudatrix. Their structures were determined by HRESI-MS and 1D and 2D NMR. Virescenosides Z4-Z8 contain rare altruronic acid 4C1 and 1C4 conformations as their carbohydrate components. Virescenosides Z5 and Z7 exhibit an unusual 16-chloro, 15-hydroxyethylgroup as their side chains.     

Citrinin derivatives from the marine-derived fungus Penicillium citrinum

Three new citrinin derivatives, penicitrinols C, D, and E (1-3), along with two known compounds, citrinin (4) and decarboxydihydrocitrinone (5), were isolated from Penicillium citrinum. Their structures were determined by spectroscopic methods and X-ray diffraction analysis. Compounds 1 and 3 demonstrated weak cytotoxicity against the HL-60 cell line.