Antimalarial Lanostane Dimers from Artificially Cultivated Fruiting Bodies of Ganoderma weberianum.

Investigation of cultivated fruiting bodies of Ganoderma weberianum led to the isolation of 11 previously unreported lanostane dimers, ganoweberianones C (3a), D (4a), E (5a), F (6a), G (7a), and H (8a) and isoganoweberianones A (1b), B (2b), D (4b), G (7b), and H (8b). Six new ganodermanontriol derivatives as three pairs of diastereomers (11/12, 13/14, and 15/16) and five new ganoweberianic acids (17-21) were also isolated. A method for semisynthesis of lanostane dimers by condensation of natural lanostanes was established, which was utilized in the structure elucidation and NMR data assignments of the undescribed natural lanostane dimers. Ganoweberianone D (4a) and isoganoweberianone D (4b) showed significant antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain) with IC50 values of 0.057 and 0.035 µM, respectively, whereas their cytotoxicity to Vero cells was weaker (IC50 8.1 and 19 µM, respectively).

Bioactive Dimeric Tetrahydroxanthones with 2,2'- and 4,4'-Axial Linkages from the Entomopathogenic Fungus Aschersonia confluens.

Thirteen tetrahydroxanthone dimers, atrop-ascherxanthone A (1), ascherxanthones C-G (2-6), and confluxanthones A-G (7-13), were isolated from the entomopathogenic fungus Aschersonia confluens BCC53152. The chemical structures were determined based on analysis of NMR spectroscopic and mass spectrometric data. The absolute configurations of compounds 1 and 7 were confirmed by single-crystal X-ray diffraction experiments, while the configurations of other compounds were assigned based upon evidence from NOESY and NOEDIFF experiments, modified Mosher's method, and ECD spectroscopic data together with biogenetic considerations. Compounds 1, 3-5, 7-11, and 13 showed antimalarial activity against Plasmodium falciparum (K1, multidrug-resistant strain) (IC50 0.6-6.1 µM), antitubercular activity against Mycobacterium tuberculosis H37Ra (MIC 6.3-25.0 µg/mL), and cytotoxicity against NCI-H187 (IC50 0.5-3.5 µM) and Vero (IC50 0.9-6.1 µM) cells. All tested compounds except for compound 9 exhibited cytotoxicity against KB cells (IC50 1.3-9.7 µM).

Highly Modified Lanostane Triterpenes from the Wood-Rot Basidiomycete Ganoderma colossus: Comparative Chemical Investigations of Natural and Artificially Cultivated Fruiting Bodies and Mycelial Cultures.

The wood-rot basidiomycete Ganoderma colossus has been chemically investigated. Comparative analyses of the natural fruiting body, artificially cultivated fruiting bodies, and mycelial cultures resulted in the isolation, in total, of 13 new highly modified lanostanes, ganocolossusins A-H (1-8) and ganodermalactones T-X (9-13), together with 23 known compounds (14-36). There were significant overlaps of the same compounds among the three different states of the fungal materials. Ganocolossusin D (4) displayed the most potent antimalarial activity against Plasmodium falciparum K1 (multi-drug-resistant strain) with an IC50 value of 2.4 µM, while it was noncytotoxic to Vero cells at 50 µg/mL.

Investigation on antimicrobial agents of the terrestrial Streptomyces sp. BCC71188.

The terrestrial actinomycete strain BCC71188 was identified as Streptomyces by its morphology (having spiral chain spore on the aerial mycelium), chemotaxonomy (containing LL-diaminopimelic acid in the cell wall), and 16S rRNA gene sequence analysis [showing high similarity values compared with Streptomyces samsunensis M1463T (99.85 %) and Streptomyces malaysiensis NBRC 16446T (99.40 %)]. The crude extract exhibited antimalarial against Plasmodium falciparum (IC50 0.19 µg/ml), anti-TB against Mycobacterial tuberculosis (MIC 6.25 µg/ml), and antibacterial against Bacillus cereus (MIC 1.56 µg/ml) activities. Therefore, chemical investigation was conducted by employing bioassay-guided method and led to the isolation of 19 compounds including two cyclic peptides (1-2), five macrolides (3-7), new naphthoquinone (8), nahuoic acid C (9), geldanamycin derivatives (10-13), cyclooctatin (14), germicidins A (15) and C (16), actinoramide A (17), abierixin, and 29-O-methylabierixin. These isolated compounds were evaluated for antimicrobial activity, such as antimalarial, anti-TB, and antibacterial activities, and for cytotoxicity against both cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells. Compounds 1-7, 10-14 exhibited antimalarial (IC50 0.22-7.14 µg/ml), and elaiophylin analogs (4-6) displayed anti-TB (MIC 0.78-12.00 µg/ml) and B. cereus (MIC 0.78-3.13 µg/ml) activities. Compounds 1, 2, 14, and abierixin displayed weak cytotoxicity, indicating a potential for antimicrobial agents.

Frenolicins H and I from the caterpillar-associated Streptomyces sp. TBRC17107.

Two undescribed frenolicins H and I (1 and 2) along with six previously described frenolicin analogues [frenolicins A (3), B (4), UCF76-B (5), E - G (6 - 8)] and two anthraquinones [3,8-dihydroxy-1-propylanthraquinone-2-carboxylic acid (9) and 3,8-dihydroxy-1-propylanthraquinone (10)] were isolated from a longkong bark eating caterpillar-derived Streptomyces sp. TBRC17107. The chemical structures were determined by NMR spectroscopic information and HRESIMS data. Frenolicins H (1) and I (2) showed weak cytotoxicity against malignant and non-malignant cells. Frenolicins A (3) and B (4) showed antimalarial activity against Plasmodium falciparum (IC50 17.4 and 1.37 µM), antibacterial activity against Bacillus cereus and Staphylococcus aureus (MIC 50.0 and 0.20 µg/mL). Only frenolicin B had anti-plant pathogenic fungal activity against Collectotrichum acutatum and Alternaria brassicicola with MIC values of MIC 1.56 and 6.25 µg/mL, respectively. Frenolicins A and G possessed anti-Mycobacterium tuberculosis with equal MICs of 25.0 µg/mL.

Lanostane triterpenoids from artificially cultivated fruiting bodies of Ganoderma cf. mastoporum.

In the quest for bioactive compounds from Ganoderma, artificially cultivated fruiting bodies of Ganoderma cf. mastoporum, strain TBRC-BCC 47851 were chemically investigated. The study led to the isolation of three undescribed lanostane triterpenoids (1-3) together with twelve known compounds. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. The new compounds were inactive in the antimalarial and antitubercular activity assays.

Lanostane triterpenoids from cultivated fruiting bodies of basidiomycete Ganoderma mbrekobenum.

In the quest for medicinally active compounds in mushrooms of the genus Ganoderma, eleven undescribed lanostane triterpenoids, including a novel chlorinated derivative, i.e., (20S,24E)-21-chloro-15ß,20,29-trihydroxy-3,7,11-trioxolanosta-8,24-dien-26-oic acid, were isolated from artificially cultivated fruiting bodies of the basidiomycete Ganoderma mbrekobenum. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. The configuration of the C-20 atom in the most abundant 20-hydroxy-lanostane, (20S,24E)-15ß,20,29-trihydroxy-3,7,11-trioxolanosta-8,24-dien-26-oic acid, was established by chemical derivatization, and the absolute configuration of the lanostane skeleton was determined by ECD calculation. Two of the undescribed compounds exhibited moderate antimalarial activity.

Benzothioate Glycoside from a terrestrial Streptomyces sp. TBRC 11511 from Thailand.

A new benzothioate glycoside metabolite, phitsanoside A, together with its new and known derivatives were isolated from Streptomyces sp. TBRC 11511 collected from sediment of a dry evergreen forest located in Phitsanulok Province, Thailand. The structure elucidation of the new compound was interpreted on the basis of spectroscopic data analysis. The configuration of the sugar moiety was derived based on NOESY nuclear magnetic resonance correlations, a vicinal coupling constant analysis, and the measurement of an optical rotation from the hydrolyzed sugar unit, which was identified as ß-D-glucopyranose. Phitsanoside A did not exhibit antibacterial activity against Bacillus cereus, Mycobacterium tuberculosis or Staphylococcus aureus, but phitsanoside B showed activity against all of them with MIC values of 3.13, 25 and 12.5 µg ml-1, respectively.

Two new drimane sesquiterpenes, fudecadiones A and B, from the soil fungus Penicillium sp. BCC 17468.

Two new drimane sesquiterpenoids, fudecadione A and fudecadione B (1, 2), together with the known brefeldin A (3) and fulvic acid (4), were isolated from the soil fungus Penicillium sp. BCC 17468. Chemical structures were determined based on spectroscopic evidence including 1D and 2D NMR and mass spectral data. The proposed relative stereochemistry of fudecadiones A and B was based upon NOESY spectral data and chemical means. Compounds 1 and 4 exhibited anticancer activity against MCF-7, KB, and NCI-H187, with IC (50) values in the range of 5.05-45.43 µg/mL, while compound 2 was inactive against these tumor cells. Brefeldin (3) also displayed antimalarial activity against PLASMODIUM FALCIPARUM (K1, multidrug-resistant strain), with an IC (50) value of 1.12 µg/mL.

Chromone derivatives, R- and S- taeniolin, from the marine-derived fungus Taeniolella sp. BCC31839.

Two unknown enantiomeric compounds, named (R)- and (S)-taeniolin, along with six known compounds, were isolated from the marine-associated fungus Taeniolella sp. BCC31839. Chemical structures were determined by NMR spectroscopic techniques, and the absolute configurations were confirmed by Mosher application together with CD spectral analyses. Both were inactive for antimicrobial activity against multidrug-resistant malaria parasite (Plasmodium falciparum) and bacteria (Mycobacerium tuberculosis and Bacillus cereus) at maximum tested concentration.

Lanostane triterpenoids from cultivated fruiting bodies of Ganoderma sichuanense: Determination of the C-25 absolute configuration of ganoderic acid A and its derivatives using the phenylglycine methyl ester (PGME) method.

Three undescribed lanostane triterpenoids, together with twenty-one known compounds, were isolated from artificially cultivated fruiting bodies of the basidiomycete Ganoderma sichuanense. The absolute configuration at C-25 of ganoderic acid A and its derivatives was determined to be 25R by application of the phenylglycine methyl ester (PGME) method. Among the isolated compounds, ganoderiol F exhibited the most potent activity against Mycobacterium tuberculosis H37Ra with an MIC value of 0.781 µg/ml.

Secondary metabolites from cultures of the ant pathogenic fungus Ophiocordyceps irangiensis BCC 2728.

Five new compounds, iranginins A-E (1-5), together with sixteen known compounds were isolated from the insect pathogenic fungus Ophiocordyceps irangiensis BCC 2728. The structures and the absolute configurations of the new compounds were established by spectroscopic analyses, the application of modified Mosher's method (for 2), ECD calculation (for 5), and X-ray crystallographic analysis (for 4). LL-Z1640-5 and mucorisocoumarin C were active against Mycobacterium tuberculosis (MIC 41.7 and 85.0 µM, respectively), while peyroisocoumarin D exhibited cytotoxic activity (IC50 65.6 µM).

Neuroprotective potential of new chromones isolated from the soil actinomycete Microbispora sp. TBRC6027.

Nine new chromone analogs (1-9) were isolated from the soil actinomycete Microbispora sp. TBRC6027. The chemical structures were determined based upon NMR spectroscopic methods. These compounds were evaluated in vitro by using P19-derived neurons for neuroprotective activity against oxidative stress induced by serum deprivation and showed % viability of neurons at the concentration of 1 ng/mL varied from 43.51% to 52.99% without significant neurotoxicity for P19-derived neurons at the same concentration. Moreover, all tested compounds were inactive for antibacterial activity against both Gram-positive and Gram-negative bacteria and for cytotoxicity against MCF-7 (human breast cancer) and Vero cells at maximum tested concentration 50 µg/mL. However, compounds 4, 6, and 7 displayed weak cytotoxicity against NCI-H187 (human small-cell lung cancer) cells with IC50 in a range of 87.99-91.57 µM.

Hopane-type triterpenes and binaphthopyrones from the scale insect pathogenic fungus Aschersonia paraphysata BCC 11964.

Two new triterpenes, 17(21)-hopene-6alpha,12beta-diol (1) and 17(21)-hopen-12beta-ol (2), the known 17(21)-hopen-6alpha-ol (zeorinin, 3), and two new biarylic dihydronaphthopyrones, aschernaphthopyrones A (4) and B (5), were isolated from the scale insect pathogenic fungus Aschersonia paraphysata BCC 11964. Hopene 1 and aschernaphthopyrone A (4) exhibited antimalarial activity with IC(50) values of 15 and 7.3 microM, respectively.

Butyrolactones from the fungus Aspergillus terreus BCC 4651.

Two new butenolides, butyrolactones VI (1) and VII (2), were isolated together with six known compounds, butyrolactones I (3), II (4), IV (5), and V (6), aspernolide B (7), and bisdethiodi(methylthio)acetylaranotin (8) from the fungus Aspergillus terreus BCC 4651. Compound 8, exhibiting a minimum inhibitory concentration (MIC) value of 1.56 µg/ml against Mycobacterium tuberculosis H37Ra, proved to be the antimycobacterial principle from the culture of this fungus. On the other hand, butyrolactone V (6) showed antiplasmodial activity against Plasmodium falciparum K1 with an IC50 of 7.9 µg/ml.

Lanostane triterpenoids from cultivated fruiting bodies of the wood-rot basidiomycete Ganoderma casuarinicola.

Sixteen previously undescribed lanostane-type triterpenoids (1-16), together with fourteen known compounds, were isolated from cultivated fruiting bodies of the basidiomycete Ganoderma casuarinicola, a recently described species. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. Two of these compounds, 9 and 10, showed antimalarial activity with IC50 values of 9.7 and 9.2 µg/ml, respectively.

Chromanones and aryl glucoside analogs from the entomopathogenic fungus Aschersonia confluens BCC53152.

Six new compounds [ascherlactones A (1) and B (2), ascherchromanone A (3), phenethyl 4'-O-methylglucoside (8), 4'-O-methylpleoside (10), and 4'-O-methyltorachrysone 8-O-glucoside (11)] and one naturally new compound [4'-O-methyl-ß-d-benzylglucoside (9)] together with fourteen known compounds, including paecilodepsipeptides A (5), B (7), and D (4), conoideocrellide A (6), eugenin (12), 5-hydroxy-2,3-dimethyl-7-methoxychromone (13), (S)-1-phenyl-1,2-ethanediol (14), (2S)-l-3-phenyllactic acid (15), papuline [or (2S)-l-3-phenyllactic acid methyl ester, 16], 2'-epi terpendole A (17), terpendoles C (18) and D (19), cholic acid, and zeorin were isolated from the entomopathogenic fungus Aschersonia confluens BCC53152. Their chemical structures were elucidated on the basis of NMR spectroscopic and mass spectrometric analyses. The absolute configurations were determined by using the evidence from NOESY correlations, chemical means, optical rotation values together with comparison of ECD spectroscopic data with the calculated ECD spectra. The plausible biosynthetic pathway of compounds 1-3 was also proposed. Moreover, antimicrobial activity such as antimalarial, antitubercular, antifungal, and antibacterial activities and cytotoxicity against cancerous (MCF-7, KB, and NCI-H187) and non-cancerous (Vero) cells of the isolated compounds were evaluated.

Isariotins E and F, spirocyclic and bicyclic hemiacetals from the entomopathogenic fungus Isaria tenuipes BCC 12625.

New spirocyclic and bicyclic hemiacetals, isariotins E (1) and F (2), together with TK-57-164A (3) were isolated from the entomopathogenic fungus Isaria tenuipes BCC 12625. The absolute configuration of 3 was addressed by application of the modified Mosher's method. Isariotin F (2) exhibited activity against the malaria parasite Plasmodium falciparum K1 with an IC(50) value of 5.1 microM and cytotoxic activities against cancer cell lines (KB, BC, and NCI-H187) and nonmalignant (Vero) cells with respective IC(50) values of 15.8, 2.4, 1.6, and 2.9 microM.

Antimicrobial activity and cytotoxicity of xanthoquinodin analogs from the fungus Cytospora eugeniae BCC42696.

Eleven previously undescribed compounds, including cytosporanthraxanthone, xanthoquinodins A7-A10, ketoxanthoquinodin A6, xanthoquinodins B6-B8, and spiroxanthoquinodins A and B, and one synthetically known compound, 2-methoxy pinselin, as well as ten known compounds, including xanthoquinodins A4-A6, B4, and B5, chrysophanol, physcion, (4S)-5-hydroxy-4-methoxy-α-tetralone, (4S)-4,8-dihydroxy-α-tetralone (or isosclerone), and gonytolide C were isolated from the fungus Cytospora eugeniae BCC42696. Their chemical structures were determined based on the analysis of NMR spectroscopic and mass spectrometric data. Moreover, the absolute configurations of the unknown compounds were established by using NOESY and NOEDIFF NMR experiments along with CD spectroscopic data. The isolated xanthoquinodins exhibited a broad range of antimalarial, antibacterial, and fungicidal activities as well as cytotoxicity. Xanthoquinodins A6, B4, and B5 showed strong activity to Plasmodium falciparum, K1 strain (IC50 0.52-0.92 µM) and displayed anti-Bacillus cereus (MIC 1.56 µg/mL). Xanthoquinodin A6 also showed anti-Curvularia lunata (MIC 3.13 µg/mL). In addition, xanthoquinodins A4, A6, B4, and B5 and ketoxanthoquinodin A6 showed cytotoxicity against both cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells.

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.