Strobiloscyphones A-F, 6-Isopentylsphaeropsidones and Other Metabolites from sp. AZ0266, a Leaf-Associated Fungus of Douglas Fir.

Six new 6-isopentylsphaeropsidones, strobiloscyphones A-F (-), and a new hexadecanoic acid, (2,4,6)-8,9-dihydroxy-10-oxohexadeca-2,4,6-trienoic acid (), together with sphaeropsidone () and its known synthetic analogue 5-dehydrosphaeropsidone () were isolated from sp. AZ0266, a fungus inhabiting the leaf litter of Douglas fir (). The structures of - were established on the basis of their high-resolution mass and 1D and 2D NMR spectroscopic data, and their relative and/or absolute configurations were determined by NOE, comparison of experimental and calculated ECD spectra, and application of the modified Mosher's ester method.

Chlorinated Dehydrocurvularins and Alterperylenepoxide A from Alternaria sp. AST0039, a Fungal Endophyte of Astragalus lentiginosus.

Investigation of Alternaria sp. AST0039, an endophytic fungus obtained from the leaf tissue of Astragalus lentiginosus, led to the isolation of (-)-(10E,15S)-4,6-dichloro-10(11)-dehydrocurvularin (1), (-)-(10E,15S)-6-chloro-10(11)-dehydrocurvularin (2), (-)-(10E,15S)-10(11)-dehydrocurvularin (3), and alterperylenepoxide A (4) together with scytalone and α-acetylorcinol. Structures of 1 and 4 were established from their spectroscopic data, and the relative configuration of 4 was determined with the help of nuclear Overhauser effect difference data.

Selective inhibition of p97 by chlorinated analogues of dehydrocurvularin.

The ATPase p97 is a ubiquitin targeted segregase that uses the energy of ATP binding and hydrolysis to extract ubiquitylated substrates from biological membranes, from other proteins, or from protein complexes to carry out myriad tasks in eukaryotes. Increased p97 activity has been linked to a poor prognosis in cancer patients, making p97 an anti-neoplastic target. In the present study, we show that dehydrocurvularin (DHC) and its chlorinated variants are covalent inhibitors of p97, interfering with its ATPase activity.

Cytotoxic Cytochalasins and Other Metabolites from Xylariaceae sp. FL0390, a Fungal Endophyte of Spanish Moss.

Two new metabolites, 6-oxo-12-norcytochalasin D (1) and 4,5-di-isobutyl-2(1H)-pyrimidinone (2), together with seven known metabolites, cytochalasins D (3), Q (4), and N (5), 12-hydroxyzygosporin G (6), heptelidic acid chlorohydrin (7), (+)-heptelidic acid (8), and trichoderonic acid A (9), were isolated from Xylariaceae sp. FL0390, a fungal endophyte inhabiting Spanish moss, Tillandsia usneoides. Metabolite 1 is the first example of a 12-norcytochalasin.

Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi.

Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, altertoxins V (1) and VI (2) together with the known compounds, altertoxins I (3), II (4), and III (5). The structures of 1 and 2 were determined by detailed spectroscopic analysis and those of 3-5 were established by comparison with reported data.

Geopyxins A-E, ent-kaurane diterpenoids from endolichenic fungal strains Geopyxis aff. majalis and Geopyxis sp. AZ0066: structure-activity relationships of geopyxins and their analogues.

Four new ent-kaurane diterpenoids, geopyxins A-D (1-4), were isolated from Geopyxis aff. majalis, a fungus occurring in the lichen Pseudevernia intensa, whereas Geopyxis sp. AZ0066 inhabiting the same host afforded two new ent-kaurane diterpenoids, geopyxins E and F (5 and 6), together with 1 and 3.

Smardaesidins A-G, isopimarane and 20-nor-isopimarane diterpenoids from Smardaea sp., a fungal endophyte of the moss Ceratodon purpureus.

Five new isopimarane diterpenes, smardaesidins A-E (1- 5) and two new 20-nor-isopimarane diterpenes, smardaesidins F (6) and G (7), together with sphaeropsidins A (8) and C-F (10-13) were isolated from an endophytic fungal strain, Smardaea sp. AZ0432, occurring in living photosynthetic tissue of the moss Ceratodon purpureus . Of these, smardaesidins B (2) and C (3) were obtained as an inseparable mixture of isomers.

Maximizing chemical diversity of fungal metabolites: biogenetically related Heptaketides of the endolichenic fungus Corynespora sp. (1).

In an attempt to explore the biosynthetic potential of the endolichenic fungus Corynespora sp. BA-10763, its metabolite profiles under several culture conditions were investigated. When cultured in potato dextrose agar, it produced three new heptaketides, 9-O-methylscytalol A (1), 7-desmethylherbarin (2), and 8-hydroxyherbarin (3), together with biogenetically related metabolites scytalol A (4), 8-O-methylfusarubin (5), scorpinone (6), and 8-O-methylbostrycoidin (7), which are new to this organism, and herbarin (8), a metabolite previously encountered in this fungal strain.

Tricinonoic acid and tricindiol, two new irregular sesquiterpenes from an endophytic strain of Fusarium tricinctum.

Two new rare irregular sesquiterpenes, tricinonoic acid (1) and tricindiol (2), and the known furanopyrrolidones, NG-391 (3) and NG-393 (4), have been isolated from an EtOAc extract of Fusarium tricinctum, a fungus endophytic in the root tissue of the Sonoran desert plant, Rumex hymenosepalus. The structures of 1 and 2 were elucidated on the basis of their high-resolution mass, 1D and 2D NMR spectroscopic data. A possible biosynthetic route to 1 and 2 from farnesyl diphosphate is proposed.

Zinagrandinolides A-C, cytotoxic delta-elemanolide-type sesquiterpene lactones from Zinnia grandiflora.

Three new delta-elemanolide-type sesquiterpene lactones, zinagrandinolides A-C (1-3), and the known delta-elemanolide 4 have been isolated by a bioassay-guided fractionation of a cytotoxic hexane extract of the aerial parts of Zinnia grandiflora. The structures of 1-3 were determined on the basis of high-resolution mass and NMR data. All compounds exhibited strong cytotoxicity against the cancer cell lines NCI-H460, MCF-7, SF-268, and MIA Pa Ca-2 and the normal human fibroblast cell type WI-38, but none showed significant selectivity.

Globosumones A-C, cytotoxic orsellinic acid esters from the Sonoran desert endophytic fungus Chaetomium globosum.

Three new esters of orsellinic acid, globosumones A-C (1-3), and three known compounds, orsellinic acid (4), orcinol, and trichodion (5), were isolated from Chaetomium globosum endophytic on Ephedrafasciculata (Mormon tea). The structures of the new compounds 1-3 were established spectroscopically, which included 2D NMR experiments and 1H NMR studies on Mosher's ester derivatives. All compounds were evaluated for inhibition of cell proliferation in a panel of four cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), SF-268 (CNS glioma), and MIA Pa Ca-2 (pancreatic carcinoma), and normal human fibroblast cells (WI-38).

Cytotoxic and other metabolites of Aspergillus inhabiting the rhizosphere of Sonoran desert plants.

In a study to discover potential anticancer agents from rhizosphere fungi of Sonoran desert plants cytotoxic EtOAc extracts of four Aspergillus strains have been investigated. Two new metabolites, terrequinone A (1) and terrefuranone (2), along with Na-acetyl aszonalemin (LL-S490beta) (3) were isolated from As. terreus occurring in the rhizosphere of Ambrosia ambrosoides, whereas As.