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.

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.

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.

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.

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].

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.

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].

A new lignan from the stem bark of Fagraea fragrans Roxb.

A new lignan, named fagraeanolide (1), and 14 known compounds were isolated from the stem bark of Fagraea fragrans Roxb. Their structures were determined by spectroscopic methods. Fagraeanolide is the first identified oxofurofuran lignan from the genus Fagraea, whileß-boswelic acid (4), gentiogenol (5), 3-(4-hydroxy-3-methoxyphenyl)-acrylic acid octacosyl ester (7) and pinoresinol (14) were isolated from this plant for the first time. The crude extract of F. fragrans was not toxic to cell lines. The isolated compounds showed no antibacterial activity.

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.

Limonoids and carbazole alkaloids from the twigs of Chalcas siamensis Tanaka.

One new limonoid, named siamensinolide (1), together with two known limonoids (2 and 3) and eight carbazole alkaloids (4-11) were isolated from the twigs of Chalcas siamensis Tanaka. Their structures were elucidated by spectroscopic methods, mainly 1D and 2D NMR spectroscopy. O-methylclausenolide (2) displayed strong cytotoxicity against A2780 cell lines with the IC50 value of 9.2 µM, while clausenolide (3) exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus with the MIC value of 0.5 µg/mL.

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.

Lovastatin Production by Aspergillus sclerotiorum Using Agricultural Waste.

RESEARCH BACKGROUND: Lovastatin is a well-known drug used to reduce hypercholesterolaemia. However, the cost of lovastatin production is still high. Therefore, alternative low-cost carbon sources for the production of lovastatin are desirable. EXPERIMENTAL APPROACH: Four different agricultural wastes, namely corn trunks, rice husks, wild sugarcane, and soya bean sludge, were tested separately as substrates to produce lovastatin using a new fungal strain, Aspergillus sclerotiorum PSU-RSPG 178, under both submerged and solid-state fermentation (SSF). RESULTS AND CONCLUSIONS: Of these substrates and cultivation systems, soya bean sludge gave the highest lovastatin yield on dry mass basis of 0.04 mg/g after 14 days of SSF at 25 °C. Therefore, the soya bean sludge was separately supplemented with glucose, wheat flour, trace elements, palm oil, urea and molasses. The addition of the palm oil enhanced the lovastatin yield to 0.99 mg/g. In addition, the optimum conditions, which gave a lovastatin yield of (20±2) mg/g after 18 days of SSF, were soya bean sludge containing 80% moisture (dry basis) at a ratio of soya bean sludge (g) to mycelial agar plugs of 1:4, and a ratio of soya bean sludge (g) to palm oil (mL) of 1:2. Besides, the lovastatin yields obtained from SSF using fresh or dry soya bean sludge were not significantly different. NOVELTY AND SCIENTIFIC CONTRIBUTION: We conclude that A. sclerotiorum PSU-RSPG 178 has a good potential as an alternative strain for producing lovastatin using soya bean sludge supplemented with palm oil as a carbon source.

Depsidones and a dihydroxanthenone from the endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261.

Three new compounds including two depsidones (simplicildones J and K) and one dihydroxanthenone (globosuxanthone E) together with nine known compounds were obtained from the crude extracts of two endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261 which were isolated from the leaves of Hevea brasiliensis. The structures were elucidated by spectroscopic evidence. The absolute configuration of globosuxanthone E was established by means of experimental and calculated TDDFT ECD data. Simplicildone K exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with equal MIC values of 128 µg/mL. Simplicildone K and globosuxanthone E displayed antifungal activity against Cryptococcus neoformans ATCC90113 with the same MIC values of 32 µg/mL. In addition, known botryohordine C and simplicildone A showed phosphodiesterase 5 inhibitory activity with the IC50 values of 5.69 and 9.96 µM, respectively, and were noncytotoxic toward noncancerous Vero cells.

Gordonia sediminis sp. nov., an actinomycete isolated from mangrove sediment.

The taxonomic position of an actinomycete designated AMA 120T, isolated from mangrove sediment, was clarified by phenotypic, chemotaxonomic and phylogenetic studies. The 16S rRNA gene sequence revealed that strain AMA 120T was most closely related to Gordonia rhizosphera NBRC 16068T (98.9 %), Gordonia polyisoprenivorans NBRC 16320T (98.1 %) and Gordonia bronchialis NBRC 16047T (98.1 %). A fragment of the gyrB gene of strain AMA 120T formed a distinct phyletic line with G. rhizosphera NBRC 16068T (95.4 %). Strain AMA 120T contained meso-diaminopimelic acid, arabinose and galactose as cell-wall components, and MK-9(H2) was the predominant menaquinone. The polar lipid profile for this strain consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and two unidentified phospholipids. Mycolic acid was present. The major fatty acids were C16 : 0, C18 : 1ω9c and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The DNA-DNA relatedness values between AMA 120T and close species were below 70 %. There was an obvious distinction in the average nucleotide identity distribution between strain AMA 120T and its closely related strains at around 75-92%. The DNA G+C content of strain AMA 120T was 66.6 mol%. These results, coupled with the phenotypic and chemotaxonomic data, indicated that strain AMA 120T represents a novel species of the genus Gordonia, for which the name Gordoniasediminis sp. nov. is proposed. The type strain is AMA 120T (=TBRC 7109T=NBRC 113236T).

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.

Semisynthesis and antibacterial activities of nidulin derivatives.

Derivatives of the fungal depsidone, nidulin, have been synthesized in order to evaluate the potential of the chemical skeleton as antibacterial agents. Alkylation, acylation, and arylation reactions of nornidulin underwent in a regioselective manner to predominantly produce 8-O-substituted derivatives. Many of the semisynthetic derivatives showed more potent antibacterial activities than nidulin, In particular, 8-O-aryl ether derivatives displayed significant activities against Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus.

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica.

In the course of our exploration of the Thai invertebrate-pathogenic fungi for biologically active metabolites, pigmentosin A (1) and a new bis(naphtho-α-pyrone) derivative, pigmentosin B (2), were isolated from the spider-associated fungus Gibellula sp. Furthermore, a new glycosylated asperfuran 3, together with one new (6) and two known (4 and 5) cyclodepsipeptides, was isolated from Cordyceps javanica. The pigmentosins 1 and 2 showed to be active against biofilm formation of Staphylococcus aureus DSM1104. The lack of toxicity toward the studied microorganism and cell lines of pigmentosin B (2), as well as the antimicrobial effect of pigmentosin A (1), made them good candidates for further development for use in combination therapy of infections involving biofilm-forming S. aureus. The structure elucidation and determination of the absolute configuration were accomplished using a combination of spectroscopy, including 1D and 2D NMR, HRMS, Mosher ester analysis, and comparison of calculated/experimental ECD spectra. A chemotaxonomic investigation of the secondary metabolite profiles using analytical HPLC coupled with diode array detection and mass spectrometry (HPLC-DAD-MS) revealed that the production of pigmentosin B (2) was apparently specific for Gibellula sp., while the glycoasperfuran 3 was specific for C. javanica.

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.

Naphthoquinones from the leaves of Rhinacanthus nasutus having acetylcholinesterase inhibitory and cytotoxic activities.

Four new naphthoquinones (1-4), named rhinacanthins S (1), T (2), U (3) and V (4), together with 13 known naphthoquinones were isolated from the leaf extract of Rhinacanthus nasutus. The structures of isolated compounds were elucidated by spectroscopic methods, especially 1D and 2D NMR spectroscopy and mass spectrometry. Rhinacanthin S (1) exhibited acetylcholinesterase inhibition activity with a % inhibition value of 48.04±3.25. The known rhinacanthin A (5) showed cytotoxicity against a MCF-7 cell line with an IC50 value of 8.79µM, while rhinacanthin N (15) was active against the NCI-H187 cell line with an IC50=2.24µM and Vero cells (IC50=3.00µM).