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.     

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.     

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).     

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.     

Halogenated anthraquinones from the marine-derived fungus Aspergillus sp. SCSIO F063

Metabolomic investigations focusing on the marine-derived fungus Aspergillus sp. SCSIO F063 have unveiled seven new chlorinated anthraquinones (1-7) related to averantin, together with five known analogues (11-15) when the fungus was fermented using sea salt-containing potato dextrose broth. Through the addition of sodium bromide to the broth, two new brominated anthraquinones (8, 9) and one new nonhalogenated anthraquinone (10) were obtained from the fungal mycelia. Their structures were elucidated by extensive spectroscopic analyses including MS and 1D and 2D NMR data. One metabolite, 6-O-methyl-7-chloroaveratin (2), displayed inhibition activity against three human tumor cell lines, SF-268, MCF-7, and NCI-H460, with IC(50) values of 7.11, 6.64, and 7.42 μM, respectively.     

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.     

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.     

Dehydroxychlorofusarielin B, an antibacterial polyoxygenated decalin derivative from the marine-derived fungus Aspergillus sp

Dehydroxychlorofusarielin B (1), a new antibacterial polyoxygenated decalin derivative, and the previously described fusarielins A (2) and B (3) have been isolated from the broth of a marine isolate of the fungus Aspergillus. The structure and absolute stereochemistry of the new compound was determined on the basis of the physicochemical data and X-ray diffraction. Compounds 1-3 exhibited a mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC values for each strain were as follows: compounds 1 and 3, 62.5 microg/mL for all strains; compound 2, 32.5 microg/mL for S. aureus and methicillin-resistant S. aureus and 62.5 microg/mL for multidrug-resistant S. aureus.     

Cytotoxic triterpenoids from Maytenus retusa

Seven new triterpenoids (1-7) and 36 known compounds were isolated from the root bark of Maytenus retusa. Their structures were determined by 1D and 2D spectroscopic studies. Several compounds were evaluated for their cytotoxicity against the human tumor cell lines HL-60 and MCF-7. Some of them were cytotoxic, with IC(50) values ranging between 0.2 and 4.7 μM.     

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.     

Cytotoxic and anti-inflammatory triterpenoids from Toona ciliata

Toonaciliatavarins A-H (1-8), including three new protolimonoids (1-3), two new tirucallane-type triterpenoids (4 and 5), and three new tetranortriterpenoids (6-8), and 10 known compounds were isolated from the stem barks of Toona ciliata Roem. var. henryi. Their structures were identified on the basis of spectroscopic analysis. The absolute configurations of 2 and 8 were determined by ECD calculation. The new isolates were evaluated for their cytotoxicities using six human cancer cell lines and also for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. Compounds 4 and 5 showed moderate cytotoxicities, and the protolimonoids (1-3) exhibited marked inhibitory effects on LPS-stimulated NO production.     

Oxygenated lanostane-type triterpenoids from the fungus ganodermalucidum

Two new triterpenoids, 20(21)-dehydrolucidenic acid A (1) and methyl 20(21)-dehydrolucidenate A (2), and five new 20-hydroxylucidenic acids, 20-hydroxylucidenic acid D(2) (3), 20-hydroxylucidenic acid F (4), 20-hydroxylucidenic acid E(2) (5), 20-hydroxylucidenic acid N (6), and 20-hydroxylucidenic acid P (7), were isolated from the fruiting body of the fungus Ganoderma ludicum, and their structures were established on the basis of spectroscopic methods.     

Protuboxepins A and B and protubonines A and B from the marine-derived fungus Aspergillus sp. SF-5044

Two new oxepin-containing (1 and 2) and two diketopiperazine-type alkaloids (3 and 4) have been isolated from an EtOAc extract of the marine-derived fungus Aspergillus sp. SF-5044. The structures of these metabolites were determined through analysis of NMR and MS data, along with Marfey's method. Compound 1 showed weak growth inhibitory activity against a small panel of cell lines.     

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.     

Cytotoxic triterpenoids from the leaves of Microtropis fokienensis

Five new triterpenoids, microfokienoxanes A-D (1-4) and 3beta,28-dihydroxy-11alpha-methoxyurs-12-ene (5), were isolated and identified from the leaves of Microtropis fokienensis, along with nine known compounds. The structures of the new compounds were elucidated by spectroscopic methods. The compounds obtained in this investigation were evaluated against a small panel of human cancer cell lines for cytotoxicity. Only compounds 3 and 5 exhibited cytotoxicity (IC50 < or = 5 microg/mL) for one or more cell lines.     

真菌萨氏曲霉D 2-6抗肿瘤活性代谢产物

 目的 阐明真菌萨氏曲霉（Aspergillus sydowi D2-6具抗肿瘤活性的次级代谢产物。方法 摇床发酵培养生产菌D 2-6,活性跟踪分离纯化D 2-6发酵液中的活性单体化合物,并根据理化性质和光谱分析(ESI-MS、UV、IR、NMR等鉴定单体化合物结构;采用细胞形态镜检、MTT方法评价单体化合物对人类慢性髓性白血病K562细胞、人肺癌A549细胞、人肝癌BEL7402细胞、人白血病HL60细胞和小鼠白血病P388细胞的抑制活性。结果 从真菌萨氏曲霉Aspergillus sydowi D 2-6发酵液中分离并鉴定了8个单体化合物,分别为5个二酮哌嗪类化合物fumitremorgin B(1、dihydroxy-fumitremorgin C(2、demethoxy-fumitremorgin C(3、fumitremorgin C(4和gliotoxin(5,1个喹啉类化合物fumiquinazoline C(6,2个杂螺环-γ-内酰胺类化合物azaspirofuran A(7和azaspirofuran B(8。化合物1～7的抗肿瘤活性检测结果显示,5对实验用肿瘤细胞的增殖抑制活性较强,对P388、A549、K562细胞的IC₅₀分别为1.47、0.10、0.57 nmol·L-1,7对P388、A549、BEL7402的IC₅₀分别为31.43、0.01、28.71 μmol·L-1,6对A549细胞的IC₅₀为42.10 μmol·L-1,而1、2、3、4对实验用肿瘤细胞无明显抑制活性(IC₅₀>100 μmol·L-1。结论 真菌萨氏曲霉Aspergillus sydowi D 2-6的主要抗肿瘤活性次级代谢物是含硫二酮哌嗪类、杂螺环-γ-内酰胺类和喹啉类化合物,其中,含硫哌嗪类化合物5对P388、A549、K562细胞的生长具有较强抑制作用,杂螺环-γ-内酰胺类化合物7对A549细胞具有选择性增殖抑制活性。     

Cytotoxic triterpenoids from Acridocarpus vivy from the Madagascar rain forest

Bioassay-guided fractionation of the cytotoxic MeOH extract obtained from Acridocarpus vivy led to the isolation of five new triterpenoids, acridocarpusic acids A-E (1-5); three known triterpenoids, moronic acid (6), ursolic acid, and oleanolic acid; and two known flavonoids, 4',5-dihydroxy-7-methoxyflavone and 4',5-dihydroxy-3',7-dimethoxyflavone. The structures of the new compounds 1-5 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. Compound 3 showed significant cytotoxic activity in the A2780 assay, with an IC50 value of 0.7 microg/mL.     

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.     

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.     

Cytotoxic oxoisoaporphine alkaloids from Menispermum dauricum

Four new oxoisoaporphine alkaloids, daurioxoisoporphines A-D (1-4), were isolated from the rhizomes of Menispermum dauricum. The structures of these alkaloids were established by spectroscopic methods. The cytotoxic evaluation of 1 and 2 is reported against four cancer cell lines.