Search

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.

Hypocrellutins A–C (1–3), 2- and 4-pyridone alkaloids, were isolated from cultures of the scale-insect pathogenic fungus Hypocrella discoidea BCC 71382. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. The absolute configuration of hypocrellutin B (2) was determined by ECD calculation. Their plausibly biosynthetic pathways are proposed. All isolated compounds were inactive in the antifungal, antimalarial, antitubercular, and cytotoxic activity assays.

Twelve new compounds, including nine tropolones, nemanolones A−I (1–9), three 7-isochromenones, nemanecins A−C (10–12), and a new naturally isolated 4-isochromanone (13), along with two known compounds, 7,8-dihydroxy-3-methyl isochroman-4-one (XJP), and chaetoquadrin F, were isolated from culture broth of the fungus Nemania sp. BCC 30850. Structures of these compounds were elucidated by NMR and MS spectroscopic analyses. Nemanolones exhibited cytotoxic activities and two of them, compounds 1 and 2, also showed antibacterial activity against Bacillus cereus and antifungal activity against Candida albicans.

Twelve 4-hydroxyquinoline derivatives ( 1 ⿿ 12 ) and three phenazine alkaloids ( 13⿿15 ) have been isolated from Pseudomonas aeruginosa BCC76810. All these compounds, except compounds 6 , 7 , 9 , and 11 , are known. The new quinolines are 2-(( Z )-undec-4⿲-enyl)-4-hydroxyquinoline ( 6 ), 2-(3⿲-(2⿲-hexylcyclopropyl)propyl)-4-hydroxyquinoline ( 7 ), 2- n- octyl-4-hydroxyquinoline N -oxide ( 9 ), and 2-(( Z )-undec-4⿲-enyl)-4-hydroxyquinoline N -oxide ( 11 ). Their structures were elucidated based on the spectroscopic information, such as 1D, 2D NMR, UV, and HRESIMS data. 4-Hydroxyquinolines ( 1 ⿿ 6 ) and 4-hydroxyquinoline- N- oxides ( 8 ⿿ 11 ) exhibited antimalarial activity against Plasmodium falciparum , K1 strain (IC 50 0.25⿿2.07 μg/mL) with moderate to weak cytotoxicity against cancerous (KB, MCF-7, NCI-H187) and non-cancerous (Vero) cells. In addition, 4-hydroxyquinoline N -oxides also displayed anti- Bacillus cereus and antioxidant activities.

A polycyclic tetrahydroxanthone, actinomadurone, was isolated from the actinomycete Actinomadura sp. BCC 35430. Its structure was elucidated by extensive spectroscopic analyses. Actinomadurone showed antifungal activities against Curvularia lunata , Alternaria brassicicola , Colletotrichum capsici , and Colletotrichum gloeosporioides ; and displayed cytotoxic activity against Vero cell lines.

Three polycyclic tetrahydroxanthones, chrestoxanthones A−C, together with known albofungin and chloroalbofungin were isolated from the actinomycete Streptomyces chrestomyceticus BCC 24770. Their structures were elucidated by extensive spectroscopic analyses. Chrestoxanthone A was active against Curvularia lunata and Alternaria brassicicola , while all other isolated metabolites displayed broad antifungal activities against C. lunata , A. brassicicola , Colletotrichum capsici , and Colletotrichum gloeosporioides.

Amethysione and amethysamide, new metabolites from Streptosporangium amethystogenes BCC 27081

Three new oxygen-bridged cyclooctadiene containing compounds, 5–7, phomoxydienes A–C, and two new dothiorelones I (8) and J (9), together with 10 known compounds were isolated from endophytic fungus, Phomopsis sp. BCC 45011. Structures were determined by NMR spectroscopic and MS spectrometric analyses. Mycoepoxydiene (1), deacetylmycoepoxydiene (2), phomoxydienes A (5) and C (7), and cytosporone E (12) displayed antimalarial and cytotoxic activities while 1893 A (3) and cytosporone P (13) showed only cytotoxic and antimalarial activity, respectively.

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.

Four new compounds ( 1 – 4 ), which were (−)-( 7R )-7- O -methylsydonic acid, gibellulic acid, gibellulins A and B, together with 14 known compounds ( 5 – 17 and orcinol) were isolated from the insect pathogenic fungus, Gibellula sp. BCC36964. The chemical structures were elucidated by employing NMR spectroscopic techniques, physico-chemical data, and chemical method. These compounds were evaluated for the biological activities including anti-bacterial, anti-phytopathogenic, anti- Herpes simplex virus-type 1 activities, and cytotoxicity against both cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells.

Thirteen bioxanthracenes, including eight new 1–8, together with twelve oxanthracenes and analogues, including nine new 9–17, and two naturally occurring 18 and 19, were isolated from insect pathogenic fungus, Conoideocrella luteorostrata Zimm. BCC 31648. Structures were determined by NMR spectroscopic and MS spectrometric analyses. Compounds 14, 17, and 18 displayed antimalarial and cytotoxic activities while compounds 2, 9, 11, 12, 15 and 19 exhibited only cytotoxic activity.

Six new compounds, an N -hydroxypyridone glucoside, orbiocrellin A ( 1 ), its aglycone orbiocrellin B ( 2 ), chromone glucosides 3 and 4 , a dihydrochromone 5a / 5b , and a chromone 6 , were isolated from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248. Orbiocrellin A ( 1 ) exhibited antimalarial activity against Plasmodium falciparum K1 (IC 50 3.1 μg/mL) while it was non-cytotoxic. In contrast, orbiocrellin B ( 2 ) showed both antimalarial (IC 50 2.1 μg/mL) and cytotoxic (NCI-H187 cells, IC 50 0.70 μg/mL) activities.

Four new streptophenazine derivatives I–L (2, 3, 4, 6), along with two known streptophenazines A (1) and B (5) were isolated from Streptomyces sp. BCC21835. The chemical structures have been determined based on NMR spectroscopic information and their optical rotation values. Apart from streptophenazines B and I, the isolated streptophenazines exhibited antibacterial activity against Bacillus cereus with IC50 in a range of 6.25–12.50 μg/mL. These streptophenazines also showed low cytotoxicity against both cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells.

Two new ascochlorin derivatives, nectchlorins A (1) and B (2), together with eight known compounds (3-10), were isolated from cultures of the leafhopper pathogen Microcera sp. BCC 17074. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. The absolute configuration of 2 was determined by application of the modified Mosher's method. The absolute configuration of LL-Z 1272α epoxide (9), which is a plausible biosynthetic precursor of ascochlorins, was established by chemical correlations. Cytotoxic activities of these ascochlorin derivatives were evaluated.

Three new isopimarane diterpenes, xylallantins A–C (1–3), a new eremophilane sesquiterpene, eremoxylarin C (7), and an O-methyl derivative of diplosporin (10), together with seven known compounds, xylarenolide (4), hymatoxins E (5) and K (6), eremoxylarin A (8), 07H239-A (9), acuminatopyrone (11), and coriloxin (12), were isolated from the fermentation broth of the wood-decay fungus Xylaria allantoidea BCC 23163. The structures were elucidated by analyses of NMR spectroscopic and mass spectrometry data. Xylallantin A (1) showed cytotoxicity to NCI-H187 cells (IC50 17 μg/ml), while eremoxylarin C (7) exhibited activity against Plasmodium falciparum K1 (IC50 3.1 μg/ml) and cytotoxicity to NCI-H187 cells (IC50 6.7 μg/ml).

Eight new compounds including 9′-[2-amino-3-(4″-O-methyl-α-rhamnopyranosyloxy) phenyl]nonanoic acid (1), 9′-[2-amino-3-(4″-O-methyl-α-ribopyranosyloxy)phenyl] nonanoic acid (2), 11′-[2-amino-3-(4″-O-methyl-α-rhamnopyranosyloxy)phenyl]undecanoic acid (3), 11′-[2-amino-3-(4″-O-methyl-α-ribopyranosyloxy)phenyl]undecanoic acid (4), 8-(4′-O-methyl-α-rhamnopyranosyloxy)-3,4-dihydroquinolin-2(1H)-one (5), 8-(4′-O-methyl-α-ribopyranosyloxy)-3,4-dihydroquinolin-2(1H)-one (6), 8-(4′-O-methyl-α-rhamnopyranosyloxy)-2-methyquinoline (7), and 8-(4′-O-methyl-α-ribopyranosyloxy)-2-methylquinoline (8) were isolated from Actinomadura sp. BCC27169. The chemical structures of these compounds were determined based on NMR and high-resolution mass spectroscopy. The absolute configurations of these monosaccharides were revealed by the hydrolysis of compounds 7 and 8. Compounds 3 and 8 exhibited antitubercular activity at MIC 50 μg/mL. Only compound 3 showed cytotoxicity against KB cell at IC50 18.63 μg/mL, while other isolated compounds were inactive at tested maximum concentration (50 μg/mL).

Many metabolites produced by various microorganisms have proven their usefulness in the area concerning human health. However, most of their diverse natural compound biosyntheses are hardly discovered. These metabolites might have specific or novel functions and these diverse active compounds can be achieved by biosynthesis, semi-biosynthesis, or chemical synthesis. A strategy to exploit the biosynthesis potential of a fungal strain is to use various culture conditions and to evaluate the chemical profiles of the culture extracts. The value of this approach was demonstrated with the fungal strain Aigialus parvus BCC 5311, producer of hypothemycin, aigialospirol, and aigialomycin A-D. The optimization of hypothemycin production and its derivative diversity by Aigialus parvus BCC 5311 was carried out using qualitative (general factorial design) and quantitative analysis (two-level fractional factorial design). Qualitative analysis revealed that soluble starch and yeast extract were shown to be the best carbon and nitrogen source respectively for the production of hypothemycin, aigialospirol and aigialomycin A-D. Quantitative analysis showed that the initial pH of culture medium is the most important factor that affects the production of hypothemycin and its derivatives (aigialospirol and aigialomycin A-D) production. Optimal medium composition used in a 5 L bioreactor generated a specific growth rate of A. parvus BCC 5311 of 0.0295 h-1, biomass yield of 1.6 g×gstarch-1, hypothemycin yield of 13.6 mg×gbiomass-1, and hypothemycin production rate of 0.6 mg×L-1×day-1. The maximum concentration of 58.0 mg×L-1 of hypothemycin was obtained at 120 h of culturing. Furthermore, the Aigialomycin A-D and Aigialospirol obtained were diversified towards various cultural conditions used. The high amount of hypothemycin produced and the diversity of derivatives obtained from this study should be useful for future mass production.

The genus Hypoxylon , a member of the family Xylariaceae, has been known to produce significant secondary metabolites in terms of chemical diversity. Moreover, the compounds isolated can also be used as chemotaxonomic characters for differentiation among the two sections, which are sect. Annulata and sect. Hypoxylon . In our continuing chemical screening programme for novel compounds, the crude extracts of H. fendleri BCC32408 gave significant chemical profiles in HPLC analyses. Thus, the chemical investigation of these crude extracts was then carried out. The investigation led to the isolation of ten previously undescribed compounds including three terphenylquinones (fendleryls A – C), one terphenyl (fendleryl D), and six novel drimane – phthalide-type lactone/isoindolinones derivatives (fendlerinines A – F) along with seven known compounds (2- O -methylatromentin, rickenyl E, atromentin, rickenyls C – D, (+)-ramulosin, and O -hydroxyphenyl acetic acid). The chemical structures were determined on the basis of spectroscopic analyses, including 1D, 2D NMR and high-resolution mass spectrometry, as well as chemical transformations. In addition, these isolated compounds were assessed for antimicrobial activity including antimalarial (against Plasmodium falciparum , K-1 strain), antifungal (against Candida albicans ), antibacterial (against Bacillus cereus ) activities. Cytotoxicity against both cancerous (KB, MCF-7, NCI-H187) and non-cancerous (Vero) cells of these compounds were also evaluated.

Nine alliacane sesquiterpenoids, inonoalliacanes A–I, were isolated from culture broth of the basidiomycete Inonotus sp. BCC 22670. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. The absolute configuration of inonoalliacane F was determined by application of the modified Mosher's method. Inonoalliacane A, the most abundant sesquiterpene constituent, exhibited moderate antibacterial activity against Bacillus cereus, whereas inonoalliacane B showed antiviral activity against herpes simplex virus type 1.

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. Graphical Abstract Electronic supplementary material The online version of this article (doi:10.1007/s13659-016-0105-7) contains supplementary material, which is available to authorized users.

Three polycyclic tetrahydroxanthones, chrestoxanthones A−C, together with known albofungin and chloroalbofungin were isolated from the actinomycete Streptomyces chrestomyceticus BCC 24770. Their structures were elucidated by extensive spectroscopic analyses. Chrestoxanthone A was active against Curvularia lunata and Alternaria brassicicola , while all other isolated metabolites displayed broad antifungal activities against C. lunata , A. brassicicola , Colletotrichum capsici , and Colletotrichum gloeosporioides.

Two new hopane-type triterpenenes, 6α,15α,22-trihydroxyhopane ( 4 ) and 3β-acetoxy-6α,22-dihydroxyhopane ( 5 ), together with the known 6α,22-dihydroxyhopane ( 1 , zeorin), 15α,22-dihydroxyhopane ( 2 , dustanin), and 3β-acetoxy-15α,22-dihydroxyhopane ( 3 ) were isolated from the scale insect pathogenic fungus Aschersonia calendulina BCC 23276. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data.

Nine new mycotoxins; five xanthones 1–5, hydroxanthone 6, and three anthraquinones 7–9, together with nine known compounds; sterigmatocystin (10), demethylsterigmatocystin (11), dihydrodemethylsterigmatocystin (12), sterigmatin (13), austocystin F (14), averufin (15), aflatoxin B1, paeciloquinone A, and zeorin, were isolated from the scale insect fungus Aschersonia coffeae Henn. BCC 28712. The structures of these compounds were elucidated using NMR spectroscopic and MS spectrometric analyses. Compounds 1–3 and 6–9 displayed cytotoxic activity while the xanthone 2 and anthraquinones 8 and 9 also showed antimalarial activity.

Three naturally new C -glycosylated benz[α]anthraquinone derivatives, urdamycinone E ( 1 ), urdamycinone G ( 2 ), dehydroxyaquayamycin ( 3 ) have been isolated from the marine Streptomycetes sp. BCC45596 . Urdamycin E ( 4 ), the possible biosynthetic precursor of 1 – 3 , has also been identified after a re-cultivation of the strain. These compounds ( 1 – 4 ) exhibited potent anti- Plasmodium palcifarum K1 strain with IC 50 values in a range of 0.0534–2.93 μg/mL and anti- Mycobacterium tuberculosis with minimum inhibition concentrations (MICs) in a range of 3.13–12.50 μg/mL. Cytotoxicity against KB, MCF-7, NCI-H187, and Vero cells was also evaluated.

Beauvericin was analyzed in three forms of the Lepidoptra pathogenic fungus Isaria tenuipes (4 isolates): (a) natural specimen, (b) cultivated synnemata on rice media, and (c) mycelia from fermentation in liquid media. Beauvericin was detected in very low amounts in all tested natural specimens. Synnemata on rice contained much higher concentrations of beauvericin than the corresponding natural materials, although the concentrations were lower than mycelia from liquid fermentation. The results casted a caution that beauvericin concentration should be carefully checked, as a possible toxic constituent, upon mass production of a selected strain of Isaria tenuipes for health food purposes.

Two new compounds 1 and 2, sporaridin and sporazepin, were isolated together with nine known compounds including antimicrobial diketopiperazines 3–6, from actinomycete, Streptrosporangium sp. BCC 24625. Structures of the new compounds, 1 and 2, were determined by NMR spectroscopic and MS spectrometric analyses.

Torrubiellones A-D (1-4), new pyridone and tetramic acid alkaloids, were isolated from the spider pathogenic fungus Torrubiella sp. BCC 2165. Torrubiellone A (1) exhibited antimalarial activity with an IC(50) value of 8.1 μM, while it showed very weak cytotoxic activity.

Five new 14-membered macrolides, hamigeromycins C–G, together with the previously described compounds, hamigeromycin A and 89-250904-F1 (radicicol analog A), were isolated from the fungus Hamigera avellanea BCC 17816. Hamigeromycins A, C, D, and E are stereoisomers differing from one another in the absolute configurations of the 4′,5′-diol moiety. Hamigeromycins F and G are unusual 5′-keto-analogs, and they are 6′-epimers to each other. The structures and the stereochemistry of the new compounds were deduced by analyses of the NMR spectroscopic and mass spectrometry data in combination with chemical means.

Investigation of the insect pathogenic fungus Torrubiella luteorostrata led to the isolation of three new macrocyclic torrubiellutins A–C (1–3) and the known pyrone diterpene 4. Structures were elucidated by spectroscopic data including 1D, 2D NMR, and MS spectral data. The absolute stereochemistry was determined by chemical means using Mosher reactions and Marfey's reagent, together with NOESY spectral data. Torrubiellutin C showed biological activities against KB, MCF-7, NCI-H187, and Vero cell lines with IC50 varying from 0.78 to 4.36 μg/mL, while compound 4 exhibited antimalaria and anti-inflammatory activity with IC50 values of 3.49 and 1.21 μg/mL, respectively.

In addition to ten known oxygen-bridged cyclooctadienes five new derivatives of the latter, phomoxydienes A—C (Ia—c) and dithiorelones (IIa,b) were isolated from title fungus.

Mycenadiols A–D (1–4, resp.), phenylglycols possessing an ethynyl or vinyl (ethenyl) group were isolated from cultures of the basidiomycete Mycena pruinosoviscida BCC 22723. The structures were elucidated on the basis of NMR-spectroscopic and mass spectrometric data. The absolute configurations of 1 and 2 were determined by synthesis. Compounds 1–4 are synthetically known, but, they have not been previously isolated from natural sources.

Three new 10-membered macrolides (1-3) have been isolated from the entomopathogenic fungus Cordyceps militaris BCC 2816, together with six known compounds, cepharosporolides C (4), E (5), and F (6), 2-carboxymethyl-4-(3'-hydroxybutyl)furan (7), cordycepin (8), and pyridine-2,6-dicarboxylic acid. The structures were determined by analysis of NMR data, and an X-ray analysis was performed to confirm the structure of 1. The antimalarial activity of 1-4 and 8 against Plasmodium falciparum K1 was evaluated.

Sterostreins F–O (1–10), 10 illudalanes and norilludalanes, were isolated from cultures of the Basidiomycete Stereum ostrea BCC 22955. Their structures were elucidated by analyses of the NMR spectroscopic and mass spectrometry data. Sterostreins M (8), N (9), and O (10) are pyridine-containing illudalanes.

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.

Investigation of the insect pathogenic fungus Torrubiella luteorostrata led to the isolation of three new macrocyclic torrubiellutins A–C (1–3) and the known pyrone diterpene 4. Structures were elucidated by spectroscopic data including 1D, 2D NMR, and MS spectral data. The absolute stereochemistry was determined by chemical means using Mosher reactions and Marfey's reagent, together with NOESY spectral data. Torrubiellutin C showed biological activities against KB, MCF-7, NCI-H187, and Vero cell lines with IC50 varying from 0.78 to 4.36 μg/mL, while compound 4 exhibited antimalaria and anti-inflammatory activity with IC50 values of 3.49 and 1.21 μg/mL, respectively.

Two novel cyclopropyl diketones, hamavellone A ( 1 ) and B ( 2 ), and two new 14-membered nonaketide macrolactones, hamigeromycin A ( 3 ) and B ( 4 ), together with six known compounds, 89-250904-F1 (radicicol analogue A, 5 ), pseurotin A ( 6 ), emodin ( 7 ), ω-hydroxyemodin ( 8 ), and emodin bianthrones ( 9 and 10 ) were isolated from the soil fungus Hamigera avellanea BCC 17816. The structures of the new compounds were defined by analysis of NMR and MS data. The absolute stereochemistry of 3 was addressed by chemical correlation to 5 . Hamavellone B ( 2 ) exhibited antimalarial activity with an IC 50 of 5.2 μg/mL, whereas it also showed comparable cytotoxicity.

Optimal fermentation conditions for enniatin production using the entomopathogenic fungus Verticillium hemipterigenum BCC 1449 have been investigated. Among various liquid media tested, highest efficiency of enniatin production was achieved by fermentation in yeast extract sucrose. Application of this condition to large-scale fermentation resulted in the isolation of three new analogs, O1, O2 and O3, which are closely related isomers that were characterized as an inseparable mixture, along with seven known enniatins.

An antimalarial macrocyclic polylactone, menisporopsin A (1), was isolated from a cell extract of the seed fungus Menisporopsis theobromae. The structure of 1 was elucidated on the basis of spectroscopic analysis and chemical transformations, with the absolute configuration established by application of the modified Mosher method and by using chiral HPLC. Menisporopsin A (1) possesses an unprecedented residue, 2,4-dihydroxy-6-(2,4-dihydroxy-n-pentyl)benzoic acid. This compound exhibited antimalarial activity, with an IC(50) value of 4.0 microg mL(-1), and antimycobacterial activity (MIC value of 50 microg mL(-1)).