Antimalarial 9-methoxystrobilurin derivatives from cultures of the basidiomycete Favolaschia minutissima.

Investigation of cultures of the basidiomycete Favolaschia minutissima TBRC-BCC 19434 led to the isolation of two undescribed ß-methoxyacrylate metabolites, 9-methoxystrobilurins R (1) and S (2), and a degraded aldehyde derivative, favodehyde E (3). 9-Methoxystrobilurin derivatives 1 and 2 exhibited significant antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain) with IC50 values of 0.12 and 0.21 µM, respectively.

Oudemansin and 9-methoxystrobilurin derivatives with antimalarial activity from cultures of the basidiomycete Favolaschia minutissima: assignments of the absolute configurations of the isoprene-derived units.

Five undescribed polyketide metabolites, oudemansins E (1), M (2), P (3), and Q (4), and 9-methoxystrobilurin I (5), were isolated from cultures of basidiomycete Favolaschia minutissima TBRC-BCC 19434. A γ-lactone derivative (6) of noroudemansin A (8), which was previously reported as a semisynthetic compound, was also isolated. The absolute configuration of the isoprene-derived moiety of the known cometabolite 9-methoxystrobilurin E (9) was determined to be 2'R,6'S by comparison of the experimental and calculated ECD data, which was correlated to the new derivative 1. These compounds exhibited antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain). A putative minor natural product, namely 9-methoxystrobilurin P (13), was prepared by semisynthesis, which exhibited significant antimalarial activity (IC50 0.086 µM).

Limonoids from fruiting bodies of the wood-rot basidiomycete Fulvifomes xylocarpicola associated with the mangrove tree Xylocarpus granatum.

Three previously undescribed limonoids, fulvifomins A-C, together with two known compounds, 6-deoxydetigloyl-swietenine acetate and methyl angolensate, were isolated from fruiting bodies of the wood-rot fungus Fulvifomes xylocarpicola (Hymenochaetaceae), growing on the mangrove tree Xylocarpus granatum (Meliaceae). The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data, and X-ray crystallographic analysis (for fulvifomin A). A number of similar limonoids have been isolated from higher plants of the family Meliaceae, including X. granatum. The present study represents a unique evidence that the associated basidiomycete also contains these limonoids. Fulvifomin B exhibited moderate antimalarial and antitubercular activites.

Antimalarial 9-Methoxystrobilurins, Oudemansins, and Related Polyketides from Cultures of Basidiomycete Favolaschia Species.

Fourteen new compounds, oudemansins 1-4, oudemansinols 5-7, favolasins 8-10, favolasinin (12), polyketides 13-15, and (R,E)-2,4-dimethyl-5-phenyl-4-pentene-2,3-diol (16), together with nine known compounds were isolated from the basidiomycete fungus Favolaschia sp. BCC 18686. Two new compounds, favolasin E (11) and 9-oxostrobilurin E (17), were isolated from the closely related organism Favolaschia calocera BCC 36684 along with nine ß-methoxyacrylate-type derivatives. Compounds in the class of oudemansins and strobilurins exhibited moderate to strong antimalarial activity with relatively low cytotoxicity against Vero cells (African green monkey kidney fibroblasts). Potent antimalarial activity was demonstrated for 9-methoxystrobilurins G, K, and E (IC50 values 0.061, 0.089, and 0.14 µM, respectively). The structure-activity relationships (SAR) for antimalarial activity is proposed on the basis of the activity of the new and several known ß-methoxyacrylate derivatives in combination with the data from previously isolated compounds. Furthermore, several compounds showed specific cytotoxicity against NCI-187 cells (human small-cell lung cancer), although the SAR was different from that for antimalarial activity.

Maleic anhydride and chromone derivatives from the endophytic fungus BCC 54265 (Botryosphaeriaceae).

A maleic anhydride derivative, botryoanhydride (1), and a chromone derivative, botryochromone (2), together with three known chromones, eugenitin (3), 6-hydroxymethyleugenin (4) and 6-methoxymethyleugenin (5), were isolated from cultures of the endophytic fungus BCC 54265 of the family Botryosphaeriaceae. The structures were elucidated on the basis of NMR, HRMS and CD data. Compound 2 showed weak cytotoxic activity to cancer cell-lines.

Hirsutane Sesquiterpenes from Cultures of the Basidiomycete Marasmiellus sp. BCC 22389.

Two new hirsutane sesquiterpenes, marasmiellins A (1) and B (2), were isolated from cultures of the basidiomycete Marasmiellus sp. BCC 22389. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. The absolute configuration of marasmiellin B was determined by application of the modified Mosher's method.

Prenylhydroquinone-Derived Secondary Metabolites from Cultures of the Basidiomycete Lentinus similis BCC 52578.

Two new prenylhydroquinone-derived compounds, Ientinospirol (1) and 1-(2,5-dihydroxyphenyl)-4-hydroxy-3-methyl-l-butanone (2), were isolated from cultures of the basidiomycete Lentinus similis BCC 52578, together with the known compounds panepoxydone (3), panepoxydione (4), isopanepoxydone (5), 2,2-dimethyl-6-hydroxy-2H-chromene (6), and (3R,4S)-3,4-dihydroxy-2,2-dimethyl-6-methoxychroman (7). Compounds 3 and 4 exhibited cytotoxicity against all cell-lines tested, while the other compounds were inactive.

Bioactive anthraquinone dimers from the leafhopper pathogenic fungus Torrubiella sp. BCC 28517.

Torrubiellins A (1) and B (2), two new dimeric anthraquinones were isolated from the leafhopper pathogenic fungus Torrubiella sp. BCC 28517. The structures of the new compounds were elucidated by analyses of the NMR spectroscopic and mass spectrometry data. Torrubiellin B (2) exhibited broad range of biological activities.

Pimarane diterpenes from the endophytic fungus Eutypella sp. BCC 13199.

Two new pimarane-type diterpenes, eutypellones A (1) and B (2), were isolated from the endophytic fungus Eutypella sp. BCC 13199. Cytotoxic activities of the pimaranes 1-5, isolated from this fungus, were evaluated.

Bioactive compounds from the scale insect pathogenic fungus Conoideocrella tenuis BCC 18627.

A new cyclohexadepsipeptide, conoideocrellide A (1), its linear derivatives, conoideocrellides B-D (2-4), three new hopane triterpenoids (5-7), two new bioxanthracenes (9 and 10), and a new isocoumarin glycoside (13) were isolated from the scale insect pathogenic fungus Conoideocrella tenuis BCC 18627. Biological activities of the new compounds were evaluated.

Gamma-lactones and ent-eudesmane sesquiterpenes from the endophytic fungus Eutypella sp. BCC 13199.

Two new gamma-lactones, eutypellins A (1) and B (2), and two ent-eudesmane sesquiterpenes, ent-4(15)-eudesmen-11-ol-1-one (3) and ent-4(15)-eudesmen-1alpha,11-diol (4), together with three known pimarane diterpenes, diaporthein B, scopararane A, and libertellenone C, were isolated from the endophytic fungus Eutypella sp. BCC 13199. The structures of these compounds were elucidated by interpretation of spectroscopic data. The absolute configuration of 4 was confirmed by application of the modified Mosher's method. Eutypellin A (1) and sesquiterpene 3 exhibited weak cytotoxic activities.

Comparison of the bioactive secondary metabolites from the scale insect pathogens, Anamorph Paecilomyces cinnamomeus, and Teleomorph Torrubiella luteorostrata.

A scale insect pathogen Paecilomyces cinnamomeus BCC 9616 and its teleomorph Torrubiella luteorostrata BCC 9617, collected on the same host specimen, were fermented and chemically explored. Both fungi produced paecilodepsipeptide A (1) and zeorin (4) as major constituents of mycelia extracts. The culture broth extract of BCC 9616 provided a known diketopiperazine, terezine D (5), and a new xanthone glycoside, norlichexanthone-6-O-beta-(4-O-methylglucopyranoside) (6). On the other hand, the broth extract of BCC 9617 contained small amounts of a new naphthopyrone glycoside, rubrofusarin-6-O-beta-(4-O-methylglucopyranoside) (7) along with 5. Structures of the new compounds, 6 and 7, were elucidated by interpretation of NMR and mass spectroscopic data. The overall results demonstrated that the metabolite profiles of the cultured anamorph (BCC 9616) and teleomorph (BCC 9617) originating from the same host specimen resemble each other closely. The (1)H-NMR spectroscopic analysis of the culture extracts from other strains of P. cinnamomeus and T. luteorostrata revealed that zeorin is the most commonly occurring fermentation product of these fungi, whereas paecilodepsipeptide A was the metabolite specific to the particular isolate BCC 9616/BCC 9617.

Paecilodepsipeptide A, an antimalarial and antitumor Cyclohexadepsipeptide from the insect pathogenic fungus Paecilomyces cinnamomeus BCC 9616.

Paecilodepsipeptide A (1), a new cyclohexadepsipeptide possessing three d-amino acid residues, together with its linear analogues paecilodepsipeptides B (2) and C (3), was isolated from the insect pathogenic fungus Paecilomyces cinnamomeus BCC 9616. Structures of these compounds were elucidated primarily by NMR and mass spectroscopic analyses. The absolute configurations of the amino acid and hydroxy acid residues of 1 were addressed by HPLC analysis of its acid hydrolyzate using a chiral column and Marfey's method. Paecilodepsipeptide A (1) showed activity against the malarial parasite Plasmodium falciparum K1 with an IC50 value of 4.9 microM. This compound also showed cytotoxicity to two cancer cell lines, KB (IC50 5.9 microM) and BC (IC50 6.6 microM); however, it was inactive against noncancerous Vero cells up to 67 microM (50 microg/mL).

Cyclohexadepsipeptides from the insect pathogenic fungus Hirsutella nivea BCC 2594.

Two new cyclohexadepsipeptides, hirsutatins A (1) and B (2), were isolated from a culture filtrate of the insect pathogenic fungus Hirsutella nivea BCC 2594. Structures of these compounds were elucidated primarily by NMR and mass spectroscopic analyses. The alpha-carbon stereochemistry of 1 was established by HPLC analysis of its acid hydrolysate using a chiral column. Hirsutatin B (2) exhibited activity against the malarial parasite Plasmodium falciparum K1 with an IC50 value of 5.8 microg/mL, while hirsutatin A (1) was inactive at a concentration of 20 microg/mL.

A cytotoxic xanthone dimer from the entomopathogenic fungus Aschersonia sp. BCC 8401.

Ascherxanthone A (1), a novel symmetrical tetrahydroxanthone dimer, was isolated from the entomopathogenic fungus Aschersonia sp. BCC 8401. The structure of 1 was elucidated by spectroscopic analysis, especially 2D-NMR. Compound 1 exhibited activity against Plasmodium falciparum K1 with an IC(50) value of 0.20 microg/mL, but it also showed cytotoxic activities against Vero cells and three tumor cell lines.

Unique diketopiperazine dimers from the insect pathogenic fungus Verticillium hemipterigenum BCC 1449.

[structure: see text]. Vertihemiptellides A (1) and B (2), unique diketopiperazine dimers, were isolated from the insect pathogenic fungus Verticillium hemipterigenum BCC 1449. Structures of these compounds were elucidated by NMR and mass spectral analysis, and the stereochemistry of 1 was determined by X-ray crystallography. The absolute stereochemistry of bisdethiodi(methylthio)-1-demethylhyalodendrin (3), previously isolated from the same fungus, was revised to the (3R,6R) configuration.