ent-Clavilactone J and Its Quinone Derivative, Meroterpenoids from the Fungus Resupinatus sp.

Metabolites 1 and 2, isolated from cultures of the basidiomycete Resupinatus sp. BCC84615, collected in a tropical forest in northeastern Thailand, showed weak antibiotic activity against Bacillus subtilis and Staphylococcus aureus and cytotoxicity against cancer cell lines. Their planar structures were elucidated by high-resolution electrospray ionization mass spectrometry and NMR spectroscopy as clavilactone J, known from the basidiomycete Ampulloclitocybe clavipes, and its new 1,4-benzoquinone derivative. A detailed analysis of the ROESY correlations in 1 confirmed the recent revision of the relative configuration of clavilactone J. However, specific rotation and Cotton effects observed by electronic circular dichroism were contrary to those of the clavilactones; thus, we assigned a rare antipodal absolute configuration.

Drimane-Type Sesquiterpenoids Derived from the Tropical Basidiomycetes Perenniporia centrali-africana and Cerrena sp. nov.

Five new drimane-type sesquiterpenoids were isolated from cultures of the tropical basidiomycetes, Perenniporia centrali-africana (originating from Kenya) and Cerrena sp. nov. (originating from Thailand). A new pereniporin A derivative (1), a new drimane-type sesquiterpene lactam (2), and the new 6,7-Dehydro-isodrimenediol (3) were isolated from P. centrali-africana. In parallel, the two new drimane-type sesquiterpene lactams 5 and 6 were isolated together with known isodrimenediol (4) from Cerrena sp. This is the first report of drimane-type sesquiterpene lactams from basidiomycetes. The structures were elucidated based on 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, in combination with high-resolution electrospray mass spectrometric (HR-ESIMS) data. The compounds were devoid of significant antimicrobial and cytotoxic activities.

Ganoweberianones A and B, Antimalarial Lanostane Dimers from Cultivated Fruiting Bodies of the Basidiomycete Ganoderma weberianum.

Two lanostane dimers, ganoweberianones A (1) and B (2), together with seven previously undescribed lanostanes, ganoweberianic acids A-G (3-9), and three known compounds (10-12), were isolated from the artificially cultivated fruiting bodies of the basidiomycete Ganoderma weberianum. Ganoweberianone A (1) exhibited significant antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain) with an IC50 value of 0.050 µM. A method for semisynthesis of 1 by condensation of the corresponding lanostane monomers and acid-catalyzed intramolecular transesterification was demonstrated.

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.

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.

Antitubercular Activity of Mycelium-Associated Ganoderma Lanostanoids.

In a continuation of our research into antitubercular lanostane triterpenoids from submerged cultures of Ganoderma species, three strains, Ganoderma orbiforme BCC 22325, Ganoderma sp. BCC 60695, and Ganoderma australe BCC 22314, have been investigated. Fourteen new lanostane triterpenoids, together with 35 known compounds, were isolated. Antitubercular activities of these mycelium-associated Ganoderma lanostanoids against Mycobacterium tuberculosis H37Ra were evaluated. Taken together with the assay data of previously isolated compounds, structure-activity relationships of the antitubercular activity are proposed. Most importantly, 3ß- and 15α-acetoxy groups were shown to be critical for antimycobacterial activity. The most potent compound was (24E)-3ß,15α-diacetoxylanosta-7,9(11),24-trien-26-oic acid (35).

Antitubercular Lanostane Triterpenes from Cultures of the Basidiomycete Ganoderma sp. BCC 16642.

Sixteen new lanostane triterpenoids (1-16), together with 26 known compounds (17-42), were isolated from cultures of the basidiomycete Ganoderma sp. BCC 16642. Antitubercular activities of these Ganoderma lanostanoids against Mycobacterium tuberculosis H37Ra were evaluated, and structure-activity relationships are proposed.

Ganopyrone A, a highly rearranged lanostane triterpenoid with antimalarial activity from artificially cultivated fruiting bodies of Ganoderma colossus.

Three previously undescribed highly modified lanostane triterpenoids, ganopyrone A, ganocolossusin I, and ganodermalactone Y, were isolated from the artificially cultivated fruiting bodies of the basidiomycete Ganoderma colossus TBRC-BCC 17711. Ganopyrone A possesses an unprecedented polycyclic carbon skeleton with an α-pyrone ring and C-18/C-23 bond. It showed antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain) with an IC50 value of 7.8 µM (positive control: dihydroartemisinin, IC50 1.4 nM), while its cytotoxicity (Vero cells) was much weaker (IC50 103 µM).

Chemical analysis and antitubercular activity evaluation of the dried mycelial powders of the basidiomycete Ganoderma australe TBRC-BCC 22314.

The isolation of lanostane triterpenoids possessing significant anti-tuberculosis (anti-TB) activity from mycelial cultures of the basidiomycete Ganoderma australe strain TBRC-BCC 22314 was previously reported. To demonstrate the potential of the dried mycelial powder for utilization in anti-TB medicinal products, its authentic chemical analysis was performed. Considering the possibility of the changes in the lanostane compositions and anti-TB activity by sterilization, both autoclave treated and non-autoclaved mycelial powder materials were chemically investigated. The study led to the identification of the lanostanes responsible for the activity of the mycelial extract against Mycobacterium tuberculosis H37Ra. The anti-TB activity of the extracts from autoclaved and non-autoclaved mycelial powders were the same (MIC 3.13 µg/mL). However, the analytical results revealed several unique chemical conversions of the lanostanes under the sterilization conditions. The most potent major lanostane, ganodermic acid S (1), was shown to be significantly active also against the extensively drug-resistant (XDR) strains of M. tuberculosis.

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.

Acetylenic sesquiterpenoids from cultures of the basidiomycete Stereum cf. hirsutum BCC 26597.

A new acetylenic sesquiterpenoid, stereyne A (1), and its acetonide derivative, stereyne B (2), were isolated from cultures of the basidiomycete Stereum cf. hirsutum BCC 26597. The structures were elucidated by spectroscopic analysis and a chemical correlation. Their absolute configurations were determined by application of the modified Mosher's method. They represent new structural type of sesquiterpenoids from Stereum.

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.

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.

Antimalarial lanostane triterpenoids from cultivated fruiting bodies of the basidiomycete Ganoderma sp.

Ten previously undescribed lanostane-type triterpenoids (1-10), together with 15 known lanostanes, were isolated from artificially cultivated fruiting bodies of the basidiomycete Ganoderma sp. BCC 21329. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data and by application of the modified Mosher's method. Compounds 1, 3, 5, and 7 showed moderate antimalarial activity (IC50 3.8-7.6 µg ml-1).

Lanostane triterpenoids from cultivated fruiting bodies of the basidiomycete Ganoderma australe.

A new lanostane triterpene (1), together with three known compounds (2-4), were isolated from cultivated fruiting bodies of the basidiomycete Ganoderma australe. The structure was elucidated on the basis of NMR spectroscopic and mass spectrometry data. The olefinic geometry of methyl australate (2) was revised from 20(22)Z to 20(22)E. These compounds (1-4) were different from the lanostanes isolated from mycelial cultures of the same strain source.

Aromadendrane and cyclofarnesane sesquiterpenoids from cultures of the basidiomycete Inonotus sp. BCC 23706.

Twelve aromadendrane sesquiterpenoids, inonotins A-L, and a previously unknown cyclofarnesane, i.e., inonofarnesane, together with two known compounds, were isolated from cultures of the wood-rotting basidiomycete Inonotus sp. BCC 23706. Inonotin I is identical to a previously reported compound with an incorrect structure. Structures of the compounds were elucidated by spectroscopic analysis and X-ray crystallography. The absolute configurations of inonotin D and inonofarnesane were determined by application of the modified Mosher's method.

Lanostane triterpenes from cultures of the Basidiomycete Ganoderma orbiforme BCC 22324.

Seven lanostane triterpenoids, ganorbiformins A-G, together with twelve known compounds, were isolated from cultures of the mushroom fungus Ganoderma orbiforme BCC 22324. Ganorbiformin A is an unusual rearranged analog, whereas the other compounds share the same lanostane skeleton with known ganoderic acids. The C-3 epimer of ganoderic acid T also exhibited significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra (MIC 1.3 µM).