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.     

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.     

Chlorohydroaspyrones A and B, antibacterial aspyrone derivatives from the marine-derived fungus Exophiala sp

Chlorohydroaspyrones A (1) and B (2), antibacterial aspyrone derivatives, and the previously described aspyrone (3), asperlactone (4), and penicillic acid (5) have been isolated from the broth of a marine isolate of the fungus Exophiala. The structure and absolute stereochemistry of the compounds were determined on the basis of the physicochemical data analysis and chemical reactions. Compounds 1 and 2 exhibited a mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC values of each strain are as follows: compound 1 showed 62.5 microg/mL for S. aureus and 125 microg/mL for methicillin-resistant S. aureus and multidrug-resistant S. aureus, and compound 2, 62.5 microg/mL for S. aureus and methicillin-resistant S. aureus and 125 microg/mL for multidrug-resistant S. aureus.     

Induced production of emericellamides A and B from the marine-derived fungus Emericella sp. in competing co-culture

Induction of the production of emericellamides A and B (1, 2), by the marine-derived fungus Emericella sp., was observed during co-culture with the marine actinomycete Salinispora arenicola. The planar structures of these new cyclic depsipeptides, which incorporate 3-hydroxy-2,4-dimethyldecanoic acid and 3-hydroxy-2,4,6-trimethyldodecanoic acid, were assigned by combined chemical and spectral methods. The absolute configurations of the amino acids, and those of the chiral centers on the side chain, were established by application of the Marfey's method, by J-based configuration analysis, and by application of the modified Mosher method. Emericellamides A and B show modest antibacterial activities against methicillin-resistant Staphylococcus aureus with MIC values of 3.8 and 6.0 microM, respectively.     

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 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.     

Epoxydons and a pyrone from the marine-derived fungus Nigrospora sp. PSU-F5

Nigrospoxydons A-C (1- 3) and nigrosporapyrone (4), four new metabolites, were isolated from the marine-derived fungus Nigrospora sp. PSU-F5 together with nine known compounds. Their structures were elucidated by spectroscopic methods, mainly 1D and 2D NMR spectroscopic techniques. The antibacterial activity against the standard Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus was evaluated.     

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 alkaloids and antibiotic nordammarane triterpenoids from the marine-derived fungus Aspergillus sydowi

Three new diketopiperazine alkaloids, 6-methoxyspirotryprostatin B (1), 18-oxotryprostatin A (2), and 14-hydroxyterezine D (3), with an oxaspiro[4.4]lactam moiety, 14-norpseurotin A (4), and the 29-nordammarane triterpenoid 6beta,16beta-diacetoxy-25-hydroxy-3,7-dioxy-29-nordammara-1,17(20)-dien-21-oic acid (5), as well as 12 known compounds (6- 17), were isolated from the ethyl acetate extract of a marine-derived fungal strain, Aspergillus sydowi PFW1-13. The structures of compounds 1- 5 were elucidated by comprehensive spectroscopic analysis. Compounds 1- 3 exhibit weak cytotoxicity against A-549 cells, with IC 50 values of 8.29, 1.28, and 7.31 microM, respectively. Compound 1 also shows slight cytotoxicity against HL-60 cells, with an IC 50 value of 9.71 microM. Compounds 4 and 5 display significant antimicrobial activities against Escherichia coli, Bacillus subtilis, and Micrococcus lysoleikticus with MICs of 3.74, 14.97, and 7.49 microM and 10.65, 5.33, and 10.65 microM, respectively.     

Mode of action of epoxyphomalins A and B and characterization of related metabolites from the marine-derived fungus Paraconiothyrium sp

Epoxyphomalins A (1) and B (2) are highly potent cytotoxic fungal metabolites. During the course of purifying larger quantities of 1 and 2 from Paraconiothyrium sp. fermentation extracts, three new epoxyphomalins (3-5) were isolated and characterized, showing modifications to the oxidation pattern of the cyclohexene moiety or of C-9 of the decalin system. IC(50) values for cytotoxicity against a panel of 36 human tumor cell lines were determined for all new compounds. Compound 4 was found to be cytotoxic particularly toward prostate PC3M (IC(50) = 0.72 μM) and bladder BXF 1218 L (IC(50) = 1.43 μM) cancer cell lines. In addition, inhibition of chymotrypsin-, caspase-, and trypsin-like activity of purified 20S proteasomes was determined for epoxyphomalins A (1) and B (2). The results indicate that compounds 1 and 2 exert their cytotoxic effect through potent inhibition of the 20S proteasome.     

海洋真菌Aspergillus sp.SCS-KFD66的次级代谢产物研究

目的对海洋真菌Aspergillus sp. SCS-KFD66发酵液中次级代谢产物进行分离鉴定,并测定其生物活性。方法采用硅胶柱色谱、SephadexLH-20凝胶柱色谱和高效液相色谱等技术对化合物进行分离纯化;运用多种波谱方法对分离所得化合物进行结构鉴定;分别采用DPPH法、Ellman比色法和PNPG法对化合物的自由基清除能力、乙酰胆碱酯酶抑制活性及α-葡萄糖苷酶抑制活性进行测试;采用96孔板微量法测定所得化合物对大肠杆菌Escherichiacoli、金黄色葡萄球菌Staphylococcus aureus、枯草芽孢杆菌Bacillus subtilis、单增李斯特菌Listeriamonocytogenes的抑制活性及最小抑菌浓度。结果从海洋真菌Aspergillus sp. SCS-KFD66发酵液中分离得到13个化合物,分别鉴定为3-epi-trans-4-hydroxylinalool-3,6-oxide(1)、trans-4-hydroxylinalool-3,6-oxide(2)、芦荟大黄素(3)、大黄素(4)、6-羟基芦荟大黄素(5)、原儿茶醛(6)、2,5-二羟基苯甲醛(7)、对羟基苯乙酸甲酯(8)、对羟基苯甲酸(9)、对羟基苯乙酸(10)、2-(4-羟苯基)乙醇(11)、对羟基反式肉桂酸(12)、反式阿魏酸(13)。活性测试结果表明化合物1、6、7、9～13都具有清除自由基活性,化合物4和6具有乙酰胆碱酯酶抑制活性,化合物6和7具有α-葡萄糖苷酶抑制活性;化合物4具有金黄色葡萄球菌和枯草芽孢杆菌抑制活性,MIC值分别为16、64μg/m L;化合物6具有抑制大肠杆菌、枯草芽孢杆菌和单增李斯特菌活性,MIC值分别为64、128和128μg/m L。结论分离得到12个已知化合物和1个新化合物,其中化合物1为新化合物,命名为曲霉呋喃醇。     

Antiprotozoal activities of heterocyclic-substituted xanthones from the marine-derived fungus Chaetomium sp

Investigations of the marine-derived fungus Chaetomium sp. led to the isolation of the new natural products chaetoxanthones A, B, and C (1-3). Compounds 1 and 2 are substituted with a dioxane/tetrahydropyran moiety rarely found in natural products. Compound 3 was identified as a chlorinated xanthone substituted with a tetrahydropyran ring. The configurational analysis of these compounds employed CD spectroscopy, modified Mosher's method, and selective NOE gradient measurements. Compound 2 showed selective activity against Plasmodium falciparum with an IC50 value of 0.5 microg/mL without being cytotoxic toward cultured eukaryotic cells. Compound 3 displayed a moderate activity against Trypanosoma cruzi with an IC50 value of 1.5 microg/mL.     

Induced production of bromomethylchlamydosporols A and B from the marine-derived fungus Fusarium tricinctum

The addition of CaBr(2) to the fermentation of a marine-derived Fusarium tricinctum resulted in production of halogenated chlamydosporol analogues. Two new antimicrobial halogenated pyranopyranones, bromomethylchlamydosporols A (1) and B (2), and two known compounds, chlamydosporol (an inseparable epimeric mixture of 7R:7S = 1:1 from (1)H NMR data) (3) and fusarielin A (4), were isolated from the culture. The structures of 1 and 2 were assigned through a combination of spectroscopic data analyses. Compounds 1-4 exhibited mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC values of each strain were as follows: compounds 1 and 2 showed an MIC of 15.6 μg/mL against S. aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus, and compounds 3 and 4 exhibited an MIC of 31.5 μg/mL against S. aureus and methicillin-resistant S. aureus and 62.5 μg/mL against multidrug-resistant S. aureus.     

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.     

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.     

New polyoxygenated farnesylcyclohexenones, deacetoxyyanuthone A and its hydro derivative from the marine-derived fungus Penicillium sp

New polyoxygenated farnesylcyclohexenones, 7-deacetoxyyanuthone A (1) and its 2,3-hydro derivative (2), were isolated together with the known farnesylquinones (3, 4) from a marine isolate of the genus Penicillium. The structures of the new deacetoxyyanuthone A (1) and its 2,3-hydro derivative (2) were assigned by spectroscopic methods, including 2D NMR and CD for the Cotton effect of alpha-epoxyketone experiments. Compounds 1 and 3 showed moderate in vitro cytotoxicity in a panel of five human tumor cell lines, and 1 also exhibited mild in vitro antibacterial activity against methicillin-resistant and multidrug-resistant Staphylococcus aureus (MIC, 50 microg/mL).     

海洋真菌Aspergillus sp.中的苯甲醛衍生物研究

目的 研究海洋真菌Aspergillus sp.的化学成分及其抗氧化活性.方法 采用硅胶柱色谱、高效液相色谱等方法进行分离纯化,以现代波谱技术和理化性质鉴定化合物的结构,并测定了所得化合物清除DPPH自由基的活性.结果 分离得到6个苯甲醛衍生物,分别鉴定为2-(E-3-庚烯基)-5-异戊烯基-3,6二羟基苯甲醛(1)、二氢金(色)灰绿曲霉素(2)、异二氢金(色)灰绿曲霉素(3)、曲霉素(4)、灰绿曲霉黄色素(5)和毛壳菌吡喃宁(6).结论 化合物1为新化合物,命名为异曲霉素,化合物1～6具有很强的清除DPPH自由基的活性.     

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.     

Acremolides A-D, lipodepsipeptides from an Australian marine-derived fungus, Acremonium sp

An Australian estuarine isolate of an Acremonium sp. (MST-MF588a) yielded the two known compounds 19- O-acetylchaetoglobosin D ( 1) and 19- O-acetylchaetoglobosin B ( 2), as the sole cytotoxic principles, along with the known aromatic metabolite RKB 3564S ( 3), and a novel family of lipodepsipeptides, acremolides A-D ( 4- 7). Structures were assigned to 4- 7 on the basis of detailed spectroscopic analysis and chemical derivatization and by application of a new C 3 Marfey's method for amino acid analysis.     

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.