Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge.

The isolation and structure determination of a new chlorinated benzophenone antibiotic, pestalone (1), is described. The new compound was produced by a cultured marine fungus only when a unicellular marine bacterium, strain CNJ-328, was co-cultured in the fungal fermentation. The fungus, isolated from the surface of the brown alga Rosenvingea sp. collected in the Bahamas Islands, was identified as an undescribed member of the genus Pestalotia. The structure of 1, initially assigned with only modest confidence by combined spectral and chemical data, was confirmed by single-crystal X-ray analysis. Pestalone (1) exhibits moderate in vitro cytotoxicity in the National Cancer Institute's 60 human tumor cell line screen (mean GI(50) = 6.0 microM). More importantly, pestalone shows potent antibiotic activity against methicillin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resistant Enterococcus faecium (MIC = 78 ng/mL), indicating that pestalone should be evaluated in advanced models of infectious disease.     

Three new cytochalasins produced by an endophytic fungus in the genus Rhinocladiella

Three new cytotoxic cytochalasins (1-3) and the previously reported cytochalasin E (4) were isolated from a culture of the endophytic fungus Rhinocladiella sp. using bioassay-guided fractionation. Extensive NMR and HRCIMS experiments identified these new compounds as 22-oxa-[12]-cytochalasins.     

Zygosporin D and two new cytochalasins produced by the fungus Metarrhizium anisopliae

Zygosporin D (3) and two new cytochalasins (4 and 5) were isolated from the culture filtrate of the fungus Metarrhizium anisopliae and characterized on the basis of their spectral data and chemical conversions. The new cytochalasins, 4 and 5, were determined to be deacetylcytochalasin C and (6R,16S,18R,21R)-18,21-dihydroxy-16, 18-dimethyl-10-phenyl[11]cytochalasa-13(E),19(E)-diene-1,7,17-trio ne, respectively. Of these three cytochalasins, only zygosporin D is an effective inhibitor of shoot elongation of rice seedlings.     

Diplopyrone,a new phytotoxic tetrahydropyranpyran-2-one produced by Diplodia mutila,a fungus pathogen of cork oak

A new phytotoxic monosubstituted tetrahydropyranpyran-2-one, named diplopyrone (1), was isolated from the liquid culture filtrates of Diplodia mutila, a plant pathogenic fungus causing a form of canker disease of cork oak (Quercus suber). Diplopyrone was characterized, using spectroscopic and chemical methods, as 6-[(1S)-1-hydroxyethyl]-2,4a,6,8a-tetrahydropyran[3,2-b]pyran-2-one. The absolute stereochemistry of the chiral secondary hydroxylated carbon (C-9), determined by application of Mosher's method, proved to be S. Diplopyrone assayed at a 0.01-0.1 mg/mL concentration range caused necrosis and wilting on cork oak cuttings. On a nonhost plant, tomato, diplopyrone caused brown discoloration or stewing on the stem.     

A chemical study of cyclic depsipeptides produced by a sponge-derived fungus

Two novel cyclic depsipeptides, guangomides A (1) and B (2), together with a new destruxin derivative (3) were isolated from the cytotoxic extract obtained from the saltwater culture of an unidentifiable sponge-derived fungus. The new structures were elucidated on the basis of analysis of extensive 1D and 2D NMR data sets, and the absolute configurations of 2S, 9S, 13S, 19S, 24R, 28R of 1 were determined on the basis of the combined X-ray and Marfey's method structure analysis. Identical absolute configurations were assumed for 2. The cytotoxicity of the extract was found to be due to brefeldin A, while 1 and 2 showed weak antibacterial activity against Staphylococcus epidermidis and Enterococcus durans.     

Indole alkaloids produced by a marine fungus isolate of Penicillium janthinellum Biourge

Three new indole alkaloids, shearinines D, E, and F (1-3), together with the known shearinine A (4) were isolated from the marine-derived strain of the fungus Penicillium janthinellum Biourge. The chemical structures of 1-4 were established by 2D NMR and HREIMS data. Shearinines A, D, and E induce apoptosis in human leukemia HL-60 cells, and shearinine E also inhibits EGF-induced malignant transformation of JB6 P+ Cl 41 cells in a soft agar.     

Periconicins, two new fusicoccane diterpenes produced by an endophytic fungus Periconia sp. with antibacterial activity

Two new fusicoccane diterpenes, named periconicins A (1) and B (2), with antibacterial activities have been isolated by bioassay-guided fractionation from an endophytic fungus Periconia sp., collected from small branches of Taxus cuspidata. The structures of the new compounds were determined by combined spectroscopic methods.     

Dicerandrols, new antibiotic and cytotoxic dimers produced by the fungus Phomopsis longicolla isolated from an endangered mint

Bioassay-guided fractionation of the organic extract from a culture of Phomopsis longicolla, an endophytic fungus of the endangered mint Dicerandra frutescens, led to the isolation of dicerandrols A, B, and C. Extensive NMR and HRFABMS experiments were used to identify these new yellow antibiotic and cytotoxic compounds as 2,2'-dimeric tetrahydroxanthones.     

Tupuseleiamides and basiliskamides,new acyldipeptides and antifungal polyketides produced in culture by a Bacillus laterosporus isolate obtained from a tropical marine habitat

Laboratory cultures of PNG 276, a Bacillus laterosporus isolate obtained from coastal waters off Papua New Guinea, have been shown to produce the novel metabolites basiliskamide A (1), basiliskamide B (2), tupuseleiamide A (3), and tupusleiamide B (4). The structures of 1 to 4 were elucidated by analysis of spectroscopic data and chemical degradation. Basiliskamides A (1) and B (2) show potent in vitro anti-Candida activity.     

Biscopyran, a phytotoxic hexasubstituted pyranopyran produced by Biscogniauxia mediterranea, a fungus pathogen of cork oak

A new phytotoxic hexasubstituted pyranopyran, biscopyran (3), was isolated together with phenylacetic acid (2) and previously isolated 5-methylmellein (1) from the liquid culture filtrates of Biscogniauxiamediterranea, a major fungal pathogen involved in oak decline in Sardinia. Biscopyran was characterized by spectroscopic methods as a new (Z)-2-methoxy-1-[7-((Z)-2-methoxybut-2-enoyl)-3,4,5,6-tetramethyl-2H,7H-pyrano[2,3-b]pyran-2-yl]but-2-en-1-one. Biscopyran assayed at 0.26-0.026 mM concentration range caused epinasty on cork oak cuttings. On a nonhost plant, tomato, biscopyran caused wilting. Phenylacetic acid, assayed at the same concentration, was toxic to Q. suber, while on tomato cuttings it induced internal tissue collapse on the stem.     

Hortein, a new natural product from the fungus Hortaea werneckii associated with the sponge Aplysina aerophoba

The fungus Hortaea werneckii isolated from the Mediterranean sponge Aplysina aerophoba, collected at Banyuls-sur-Mer in southern France, yielded a new compound named hortein (1), which possesses a unique ring system hitherto unknown for natural products. The structure of 1 was established on the basis of 1D and 2D NMR spectroscopic and mass spectrometric (ESI, CI, FAB, EI) data.     

A new macrocyclic trichothecene, 12,13-deoxyroridin E, produced by the marine-derived fungus Myrothecium roridum collected in Palau

A new macrocyclic trichothecene, 12,13-deoxyroridin E (1), and three known compounds, roridin E (2), verrucarin A (3), and verrucarin J (4), were obtained as cytotoxic components from the marine-derived fungus Myrothecium roridum, isolated in Palau. 12,13-Deoxyroridin E is the second example of a macrocyclic trichothecene possessing a double bond at C-12-C-13 and was about 80-fold less cytotoxic than roridin E, the epoxide variant.     

Septocylindrins A and B: peptaibols produced by the terrestrial fungus Septocylindrium sp. LL-Z1518

Two new peptaibols, septocylindrin A (1) and septocylindrin B (2), related to the well-studied membrane-channel-forming peptaibol alamethicin, were obtained from a terrestrial isolate of the fungus Septocylindrium sp. Both 1 and 2 are linear 19-amino acid peptides with a modified phenylalanine C-terminus. Analysis of the HRMS data indicated that they differ only in the 18th residue, where 1 contains Glu and 2 contains Gln. The structures of these two peptaibols were determined by extensive NMR and HRMS analysis. The absolute configurations of amino acids present in 1 were determined using Marfey's methodology. Both compounds were isolated through bioassay-guided fractionation and exhibited significant antibacterial and antifungal activity.     

Antimalarial dihydroisocoumarins produced by Geotrichum sp., an endophytic fungus of Crassocephalum crepidioides

Three novel dihydroisocoumarin derivatives (1-3) with antimalarial, antituberculous, and antifungal activities have been isolated by bioassay-guided fractionation from an endophytic fungus, Geotrichum sp., collected from Crassocephalum crepidioides. Structures were established as 7-butyl-6,8-dihydroxy-3(R)-pent-11-enylisochroman-1-one (1), 7-but-15-enyl-6,8-dihydroxy-3(R)-pent-11-enylisochroman-1-one (2), and 7-butyl-6,8-dihydroxy-3(R)-pentylisochroman-1-one (3) using spectroscopic data.     

Agonodepsides a and B: two new depsides from a filamentous fungus F7524

Two new compounds, agonodepsides A (1) and B (2), were isolated from a nonsporulating filamentous fungus, F7524. The compounds were purified via reversed-phase chromatography and their structures determined by spectroscopic methods. Agonodepside A (1) was found to inhibit the mycobacterial InhA enzyme with an IC50 value of 75 microM, while 2 was inactive at 100 microM.     

Petrobactin sulfonate, a new siderophore produced by the marine bacterium Marinobacter hydrocarbonoclasticus

Culture of the oil-degrading marine bacterium Marinobacter hydrocarbonoclasticus gave the known siderophore petrobactin (1) and the new metabolite petrobactin sulfonate (2), the first marine siderophore containing a sulfonated 3,4-dihydroxy aromatic ring. The structure of petrobactin sulfonate was elucidated from spectral data, resulting in a revision of the NMR assignments of petrobactin.     

Arenaric acid, a new pentacyclic polyether produced by a marine bacterium (Actinomycetales)

Arenaric acid (1a), a new pentacyclic polyether related to the antibiotics K-41A and oxolonomycin, was isolated as its sodium salt (1b) from the culture broth of an estuarine bacterial isolate of the genus Streptomyces. The structure of arenaric acid was established by spectroscopic methods involving comprehensive 2D NMR measurements.     

New natural products from the sponge-derived fungus Aspergillus niger

Fractionation of the EtOAc extract of a static culture of Aspergillus niger isolated from the Mediterranean sponge Axinella damicornis yielded eight secondary metabolites, out of which seven compounds (2-8) proved to be new natural products, whereas one was identified as the known fungal pigment cycloleucomelone (1). The new compounds included the 3,3'-bicoumarin bicoumanigrin (2), the structurally unusual 4-benzyl-1H-pyridin-6-one derivatives aspernigrins A and B (3 and 4), and pyranonigrins A-D (5-8), the latter featuring a novel pyrano[3,2-b]pyrrole skeleton hitherto unprecedented in nature. All structures were elucidated on the basis of extensive one- and two-dimensional NMR spectroscopic studies ((1)H, (13)C, COSY, HMQC, HMBC, NOE difference spectra) and mass spectral analysis. For the two chiral molecules 4 and 5, the absolute configurations were established by quantum chemical calculations of their circular dichroism (CD) spectra. In each case, two independent methods, i.e., a molecular dynamics approach taking into consideration the molecular flexibility, and a conformational analysis followed by Boltzmann weighting of the single CD spectra calculated for the conformers thus obtained, led to identical results without the need of any empirical comparison of chiroptical data reported for reference compounds. Bicoumanigrin (2) showed moderate cytotoxicity against human cancer cell lines in vitro. In addition, aspernigrin B (4) was found to display a strong neuroprotective effect against glutamic acid.     

Circumdatin G, a new alkaloid from the fungus Aspergillus ochraceus

The crude extract of the broth of Aspergillus ochraceus was found to inhibit the final stage of polyprotein processing during hepatitis C virus replication. Bioassay-guided fractionation led to the isolation of the known compound mellein as the active component of the extract. Also isolated were circumdatin F and a new alkaloid, circumdatin G. The structure of circumdatin G was determined by spectroscopic analysis.     

Tolaasins A--E, five new lipodepsipeptides produced by Pseudomonas tolaasii

Pseudomonas tolaasii, the causal organism of brown blotch disease of Agaricus bisporus and of the yellowing of Pleurotus ostreatus, was shown to produce in culture tolaasin I (1), tolaasin II (2), and five other minor metabolites, tolaasins A, B, C, D, and E (3-7). These compounds were demonstrated to be important in the development of the disease symptoms. This paper reports on the structural elucidation, based essentially on NMR studies and MS spectra, and biological activity of the above lipodepsipeptides (3-7). All the above analogues showed differences in the peptide moiety, as observed in other lipodepsipeptides of bacterial origin, and maintained the beta-hydroxyoctanoyl phi chain at the N-terminus, except tolaasin A, in which the acyl moiety was a gamma-carboxybutanoyl phi moiety. Among the target microorganisms used (fungi, yeast, and bacteria) the Gram-positive bacteria were the most sensitive, although the antimicrobial activity appeared to be correlated to the structural modification in the different analogues. The structure-activity relationships of these toxins are discussed.