Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346.

Two new sesquiterpenes, trichocitrinovirenes A (1) and B (2), and five known compounds including four structurally related sesquiterpenes and one γ-lactone were isolated from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346. The structures were identified by analysis of their spectroscopic data. The relative configuration was assigned based on NOEDIFF data. The absolute configuration of compound 1 was established according to specific rotations and ECD data while that of compound 2 was proposed based on biosynthetic considerations. Compound 2 possesses a rare bicyclic sesquiterpene skeleton. The antimicrobial and cytotoxic activities of the isolated compounds were evaluated.

Antibacterial and Antifungal Polyketides from the Fungus Aspergillus unguis PSU-MF16.

Seven new polyketides including a phenol (1), two diphenyl ethers (2 and 3), two depsidones (4 and 5), and two phthalides (6 and 7) were isolated from the fungus Aspergillus unguis PSU-MF16 along with 27 known compounds. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of 1 and 4-7 were established using comparative analyses of calculated and experimental ECD spectra. Among the new metabolites, 2 exhibited the best antimicrobial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and Microsporum gypseum with equal MIC values of 16 µg/mL. In addition, known emeguisin A displayed potent antimicrobial activity against S. aureus, methicillin-resistant S. aureus, and Cryptococcus neoformans with equal MIC values of 0.5 µg/mL, compared with the standard drugs, vancomycin and amphotericin B. The structure-activity relationship study of the isolated compounds for antimicrobial activity is discussed.

Trichothecenes from a Soil-Derived Trichoderma brevicompactum.

Six new (1-6), together with seven known (7-13), trichothecenes were isolated from the soil-derived Trichoderma brevicompactum PSU-RSPG27. Their structures were established using spectroscopic data. The structure of 1 was confirmed by X-ray data. Trichodermin (7) exhibited the most potent activity against Plasmodium falciparum (K1 strain) with an IC50 value of 0.1 µM, while other trichothecenes (1, 8, 9, and 12) were much less active, with IC50 values in the range of 7.1-9.6 µM. Compound 7 displayed activity against noncancerous Vero cells with an IC50 value of 0.4 µM. The remaining compounds showed moderate to weak activity, with IC50 values in the range of 6.9-15.3 µM. Compounds 7 and 12 were active against human oral carcinoma (KB) cells with IC50 values of 2.4 and 3.7 µM, respectively. Additionally, compounds 7 and 12 displayed antifungal activity against Candida albicans with the respective MIC values of 1 and 2 µg/mL and were active against Cryptococcus neoformans with equal MIC values of 4 µg/mL.

Asperidines A-C, pyrrolidine and piperidine derivatives from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178.

One new pyrrolidine derivative, asperidine A (1), and two new piperidine derivatives, asperidines B (2) and C (3), were isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178 together with two known alkaloids. Compound 3 possessed an unprecedented 7-oxa-1-azabicyclo[3.2.1]octane skeleton with four chiral centers. Their structures were determined by spectroscopic evidence. The absolute configurations of compounds 2 and 3 were established using Mosher's method and further confirmed for compound 3 by X-ray crystallographic data. Compound 2 dose-dependently inhibited the CFTR-mediated chloride secretion in T84 cells with an IC50 value of 0.96 µM whereas 3 displayed the same activity with the IC50 value of 58.62 µM. Compounds 2 and 3 also significantly reduced intracellular ROS under both normal and H2O2-treated conditions compared with their respective controls in a dose-dependent manner without cytotoxic effect on Caco-2 cells. In addition, compound 3 was inactive against noncancerous Vero cells whereas compound 2 was considered to be inactive with the IC50 value of >10 µM.

Lovastatin Analogues from the Soil-Derived Fungus Aspergillus sclerotiorum PSU-RSPG178.

Three new lovastatin analogues (1, 4, and 5) together with four known lovastatin derivatives, namely, lovastatin (2), α,ß-dehydrolovastatin (3), α,ß-dehydrodihydromonacolin K (6), and α,ß-dehydro-4a,5-dihydromonacolin L (7), were isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178. Their structures were established using spectroscopic evidence. Compound 5 exhibited the most potent activity against HMG-CoA reductase, with an IC50 value of 387 µM. In addition, the present study indicated the direct interaction of compound 5 with HMG-CoA reductase. Compound 5 was considered to be noncytotoxic against noncancerous Vero cells, with an IC50 value of 40.0 µM, whereas compound 2 displayed much stronger activity, with an IC50 value of 2.2 µM.

Eremophilane Sesquiterpenes and Diphenyl Thioethers from the Soil Fungus Penicillium copticola PSU-RSPG138.

Four new compounds including two eremophilane sesquiterpenes, penicilleremophilanes A (1) and B (2), as well as two sulfur-containing biphenols, penicillithiophenols A (3) and B (4), were isolated from the soil fungus Penicillium copticola PSU-RSPG138 together with 16 known compounds. Their structures were elucidated by spectroscopic methods. Known sporogen AO-1 exhibited significant antimalarial activity against Plasmodium falciparum with an IC50 value of 1.53 µM and cytotoxic activity to noncancerous (Vero) cell lines with an IC50 value of 4.23 µM. Although compound 1 was approximately half as active against P. falciparum with the IC50 value of 3.45 µM, it showed much weaker cytotoxic activity.

γ-Butyrolactone, cytochalasin, cyclic carbonate, eutypinic acid, and phenalenone derivatives from the soil fungus Aspergillus sp. PSU-RSPG185.

Purification of an extract from the broth of the soil fungus Aspergillus sp. PSU-RSPG185 resulted in the isolation of two new cyclic carbonate derivatives, aspergillusols A (1) and B (2), and one new eutypinic acid derivative, aspergillusic acid (3), along with six known secondary metabolites. Compounds 1 and 2 contain an unusual cyclic-carbonate functionality. In addition, the mycelial extract afforded two new phenalenones, aspergillussanones A (4) and B (5), one new cytochalasin, aspergilluchalasin (6), and one new γ-butyrolactone, aspergillulactone (7). Their structures were established by interpretation of spectroscopic evidence. Compound 4 exhibited weak activity toward KB and Vero cells with IC50 values of 48.4 and 34.2 µM, respectively.

Penicitrisochromans A-C, new isochromans from the marine-derived fungus Penicillium citrinum PSU-MF100.

Three new isochroman derivatives, penicitrisochromans A-C (1-3), together with 25 known polyketides were isolated from the marine-derived fungus Penicillium citrinum PSU-MF100. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of 1 and 2 were established by comparison of specific rotations and electronic circular dichroism (ECD) data with those of the known co-metabolite whereas those of 3 were assigned based on the ECD calculation and biosynthetic consideration. Among the isolated polyketides, three known anthraquinone derivatives, ω-hydroxyemodin, penicillanthranin A and emodin, displayed moderate to strong antibacterial activity against methicillin-resistant Staphylococcus aureus with MIC values of 32, 16 and 4 µg/mL, respectively. For antifungal activity, two known benzopyranones, coniochaetones A and C, exhibited moderate antifungal activity against Candida albicans NCPF3153 and Cryptococcus neoformans ATCC90112 with the respective MIC values of 16 and 64 µg/mL.

Furanone, morpholinone and tetrahydrofuran derivatives from the marine-derived fungus Talaromyces sp. PSU-MF07.

Three new compounds including one furanone, one morpholinone and one tetrahydrofuran together with three known compounds were isolated from the broth extract of the marine-derived fungus Talaromyces sp. PSU-MF07. The structures of the isolated compounds were determined on the basis of spectroscopic methods. The relative configuration was assigned using NOEDIFF data whereas the absolute configurations were established by Mosher's method, specific rotations and electronic circular dichroism (ECD) data. Some isolated compounds were tested for antimicrobial activity. Only known penioxalicin exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus SK1 with an MIC value of 200 µg/mL.

A nonadride derivative from the marine-derived fungus Aspergillus chevalieri PSU-AMF79.

One new nonadride enantiomer, ent-epiheveadride, along with five known dioxopiperazine derivatives were isolated from the marine-derived fungus Aspergillus chevalieri PSU-AMF79. Their structures were identified by extensive spectroscopic analysis. The absolute configuration of ent-epiheveadride was determined by comparison of the specific rotation and electronic circular dichroism data with those of related known compounds. It exhibited antifungal activity against Cryptococcus neoformans ATCC90113 flucytosine-resistant and Candida albicans NCPF3153 with the MIC values of 128 and 200 µg/mL, respectively. In addition, the known L-alanyl-L-tryptophan anhydride displayed TMEM16A inhibitory activity with 65.0% inhibition at a concentration of 5 µg/mL.

Talarostatin, a vermistatin derivative from the soil-derived fungus Talaromyces thailandensis PSU-SPSF059.

The soil-derived fungus Talaromyces thailandensis PSU-SPSF059 produced one new vermistatin derivative, talarostatin, and seven known compounds including two vermistatins, two chrodrimanins, two diphenyl ethers and one penicillide derivative. Extensive spectroscopic analysis was performed to identify their structures. The absolute configuration of talarostatin was determined by comparing the experimental and calculated electronic circular dichroism data. The antimicrobial and cytotoxic activities of the isolated secondary metabolites were also evaluated.

Phthalide and isocoumarin derivatives produced by an Acremonium sp. isolated from a mangrove Rhizophora apiculata.

Nine new fungal metabolites, one phthalide derivative, acremonide (1), and eight isocoumarin derivatives, acremonones A-H (2-9), were isolated from the mangrove-derived fungus Acremonium sp. PSU-MA70 together with 10 known compounds. Their structures were determined by NMR analysis. The known 8-deoxytrichothecin and trichodermol exhibited moderate antifungal activity against Candida albicans and Cryptococcus neoformanns, respectively.

New aromatic polyketides from the marine-derived fungus Pseudopithomyces maydicus PSU-AMF350 and their antimicrobial activity.

Four new aromatic polyketides including two diphenyl ethers (pseudopithoethers A-B, 1-2), one benzofuranone (pseudopithonone, 3) and one xanthone (pseudopithoxanthone, 4), along with two known compounds (5-6) and one new naturally occurring hydroquinone (α,2,5-trihydroxyacetophenone, 7) were isolated from the marine-derived fungus Pseudopithomyces maydicus PSU-AMF350. Their structures were identified by analysis of spectroscopic data. All isolated compounds were tested for antimicrobial activity. Only compound 7 displayed antibacterial activity against methicillin-resistant Staphylococcus aureus with the MIC value of 128 µg/mL and against S. aureus, Acinetobacter baumannii NPRC005 and A. baumannii NPRC007 with the same MIC value of 200 µg/mL.[Formula: see text].

2-Oxaspiro[4.5]decane and α-pyrenocine derivatives from the endophytic fungus Roussoella sp. PSU-H51.

One new 2-oxaspiro[4.5]decane, roussoellide, and one new α-pyrenocine, 2',3'-dihydropyrenocine A, together with nine known compounds including known arthropsolide A, and pyrenocines A and E, were obtained from the culture broth of the endophytic fungus Roussoella sp. Their structures were determined using spectroscopic data. The absolute configuration of known arthropsolide A was assigned on the basis of X-ray diffraction data using Cu Kα radiation. Known pyrenocine A displayed weak cytotoxic activity against breast cancer (MCF-7) cells with an IC50 value of 27.1 µM and weak antifungal activity against Microsporum gypseum SH-MU-4 with an MIC value of 615.2 µM.[Formula: see text].

Dimeric γ-lactone derivatives from the soil-derived fungus Lasiodiplodia theobromae NSTRU-PN1.4.

Investigation of the soil-derived fungus Lasiodiplodia theobromae NSTRU-PN1.4 resulted in the isolation of five dimeric γ-lactones including two new botryosphaerilactones D and E (4 and 5) and three known structurally related analogoues (1-3) along with seven known compounds. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 1-5 was determined by comparison of the ECD data with those of the structurally related monomeric γ-lactones. For biological evaluation, this is the first report on antifungal activity of the known (3 R,4R)-4-acetyl-3-methyl-2(3H)-dihydrofuranone which displayed weak antifungal activity against Cryptococcus neoformans with an MIC value of 200 µg/mL.

α-Pyrone and decalin derivatives from the marine-derived fungus Trichoderma harzianum PSU-MF79.

Two new compounds, one α-pyrone (trichoharzianone) and one decalin (trichoharzianin), along with eight known compounds including three decalins, two δ-lactones, two carboxylic acids and one isochroman were isolated from the marine-derived fungus Trichoderma harzianum PSU-MF79. The structures were determined by spectroscopic methods. The relative configuration of trichoharzianin was assigned based on NOEDIFF data and coupling constants whereas the absolute configurations were established by comparison of electronic circular dichroism data with those of the co-metabolites. Known (-)-massoia lactone exhibited mild antifungal activity against Cryptococcus neoformans ATCC90113 flucytosine-resistant, Candida albicans ATCC90028 and C. albicans NCPF3153 with MIC values of 128, 200 and 200 µg/mL, respectively, and weak cytotoxic activity against HCT-116 and MCF-7 cell lines with the respective IC50 values of 17 and 32 µM. In addition, it was noncytotoxic against noncancerous Vero cells with an IC50 value of >100 µM.

Morphology, Phenotype, and Molecular Identification of Clinical and Environmental Fusarium solani Species Complex Isolates from Malaysia.

Fusarium infections in humans (fusariosis) and in economically important plants involve species of several Fusarium species complexes. Species of the Fusarium solani species complex (FSSC) are the most frequent cause of human fusariosis. The FSSC comprises more than 60 closely related species that can be separated into three major clades by multi-locus sequence typing (MLST) using translation elongation factor 1-alpha (TEF1-α) and RNA polymerase II (RPB2) DNA sequences. The MLST nomenclature for clade 3 of the FSSC assigns numbers to species types (e.g., FSSC 2) and lowercase letters to identify unique haplotypes. The aim of this study was to analyse the genotypic and phenotypic characteristics of 15 environmental and 15 clinical FSSC isolates from Malaysia. MLST was used for the genotypic characterisation of FSSC isolates from various locations within Malaysia, which was complemented by their morphological characterisation on potato dextrose and carnation leaf agar. MLST identified eight different FSSC species: thirteen Fusarium keratoplasticum (i.e., FSSC 2), six Fusarium suttonianum (FSSC 20), five Fusarium falciforme (FSSC 3+4), two Fusarium cyanescens (FSSC 27), and one each of Fusarium petroliphilum (FSSC 1), Fusarium waltergamsii (FSSC 7), Fusarium sp. (FSSC 12), and Fusarium striatum (FSSC 21). Consistent with previous reports from Malaysia, most (11 of 15) clinical FSSC isolates were F. keratoplasticum and the majority (9 of 15) of environmental isolates were F. suttonianum (5) or F. falciforme (4) strains. The taxonomic relationships of the isolates were resolved phylogenetically. The eight Fusarium species also showed distinct morphological characteristics, but these were less clearly defined and reached across species boundaries. Although TEF1-α and RPB2 sequences were sufficient for the species identification of most FSSC isolates, a more precise MLST scheme needs to be established to reliably assign individual isolates of the species-rich FSSC to their geographically-, epidemiologically-, and host-associated sub-lineages.

Sesquiterpene and xanthone derivatives from the sea fan-derived fungus Aspergillus sydowii PSU-F154.

Three new sesquiterpenes, named aspergillusenes A and B and (+)-(7S)-7-O-methylsydonic acid, and two new hydrogenated xanthone derivatives, named aspergillusones A and B, were isolated from the sea fan-derived fungus Aspergillus sydowii PSU-F154 together with 10 known compounds. Their structures were identified on the basis of spectroscopic data. The isolated compounds were evaluated for their antioxidant activity.

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.

Anthraquinone, cyclopentanone, and naphthoquinone derivatives from the sea fan-derived fungi Fusarium spp. PSU-F14 and PSU-F135.

Five new metabolites, fusaranthraquinone (1), fusarnaphthoquinones A-C (2-4), and fusarone (5), were isolated from the sea fan-derived fungi Fusarium spp. PSU-F14 and PSU-F135 along with 18 known compounds. The structures were elucidated on the basis of spectroscopic evidence. Their antibacterial, antifungal, antimycobacterial, antimalarial, and cytotoxic activities were examined.