Chaetonigrisins A-L, a group of 3-Indole-1,2-Propanediol derived alkaloids from Chaetomium nigricolor YT-2.

Thirteen new alkaloids (1-13) as well as ten known compounds were isolated from the solid-state fermented rice medium of the fungus Chaetomium nigricolor YT-2. Their structures were elucidated on the basis of spectroscopic data, quantum calculations, and single crystal X-ray crystallographic analysis. Chaetonigrisin A (1) represents an unprecedented carbon skeleton featuring a polycyclic 1H-pyrano[3,2:3,4-]​furo[2,​3-​b]​indole. Chaetonigrisin B (2) displays a unique carbon skeleton with a 1,3­dioxolane bridged-ring. Chaetonigrisin C (3) is a spirocyclic indole alkaloid. Chaetonigrisins D-H (4-8) are a group of asymmetric dimers, formed with two 3-indol-3yl-1,2-propanediol (4-6) or with a 3-indol-3yl-1,2-propanediol and a 3-indol-2yl-1,2-propanediol (7-8) by a pyran ring. Chaetonigrisins I-L (9-12) each contains a 3-indol-3yl-1,2-propanediol or 3-indol-2yl-1,2-propanediol substructure. Chaetonigrisin M (13) is a new quinoline alkaloid. The neuroprotective activity assay showed that at the concentration of 40 µM, compounds (4-7, 11, and 12) improved the cell viability of PC12 cells were 49.26 %, 74.69 %, 74.76 %, 86.63 %, 66.89 %, and 69.92 %, respectively induced by 6-OHDA, compound 7 showed significant neuroprotective activity via upregulation of SOD1 mRNA and Bcl-2 mRNA.

Indole Alkaloids from Chaetomium globosum.

Two new indole alkaloids chaetocochin J (1) and chaetoglobinol A (8), along with chetomin (2), chetoseminudin A (3), cochliodinol (9), and semicochliodinol (10), were isolated from the rice culture of the fungus Chaetomium globosum. Their structures were elucidated by spectral analysis. Three new epipolythiodioxopiperazines, chaetocochins G-I (5-7), were identified by the combination of UPLC and mass spectrometric analysis. Chaetocochin I contained two sulfur bridges, one formed by three sulfur atoms between C-3 and C-11a, and the other formed by four sulfur atoms between C-3' and C-6'. Chaetocochin I was readily transformed into chetomin (2), chetoseminudin A (3), chaetocochin D (4), chaetocochin G (5), and chaetocochin H (6) by losing sulfur atoms. Compounds 1-3, and 8 exhibited antibacterial activities against Bacillus subtilis with MICs of 25, 0.78, 0.78, and 50 µg/mL, respectively, but not against Gram-negative bacterium (Escherichia coli). Compounds 2 and 8 were inactive against Candida albicans, Fusarium graminearum, Fusarium vasinfectum, Saccharomyces cerevisiae, and Aspergillus niger even at the high concentrations of 200 and 100 µg/mL, respectively. Compound 8 showed free radical scavenging capacity against the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical (ABTS(+•)), with IC50 values of 143.6 and 45.2 µM, respectively. The free radical scavenging capacity rates of compounds 1-3 on the DPPH and ABTS(+•) were less than 20% at the test concentrations (89.9-108.3 µM). The superoxide anion radical scavenging assay indicated that compounds 1-3, and 8 showed 14.8% (90.9 µM), 18.1% (90.9 µM), 51.5% (88.3 µM), and 30.4% (61.3 µM) superoxide anion radical scavenging capacity, respectively.

Chaetomadramines A-E, a class of siderophores with potent neuroprotective activity from the fungus Chaetomium madrasense cib-1.

Five hydroxamate siderophores, chaetomadramines A-E (1-5), along with seven known compounds were isolated from the fermented rice culture of the fungus Chaetomium madrasense cib-1. Compounds 1-5 were structurally elucidated on the basis of spectroscopic data, which were a group of unusual hydroxamate siderophores, bearing a long fatty acyl on the α-NH2 of the Nδ-hydroxylated ornithine. Compounds 2-5 were new. The structural elucidation and spectroscopic data of 1 were reported for the first time. Compounds 2-4 significantly improved the survival rates of PC12 cells in the neuroprotective activity assay at the concentration of 40 µM.

Biosensor-Enabled Discovery of CaERG6 Inhibitors and Their Antifungal Mode of Action against Candida albicans.

Fungal infections caused by opportunistic pathogens, such as Candida albicans, are generally underappreciated by the public in spite of their high mortality rates. Antifungal arsenals are extremely limited. Herein, based on biosynthetic pathway comparison and functional characterization, CaERG6, a crucial sterol 24-C-methyltransferase involved in the biosynthesis of ubiquitous ergosterol in C. albicans, was set up as an antifungal target. CaERG6 inhibitors were identified from the in-house small-molecule library by a biosensor-based high-throughput screening. The CaERG6 inhibitor NP256 (palustrisoic acid E) is a potential antifungal natural product that acts by inhibiting ergosterol biosynthesis, downregulating the gene expression level in hyphal formation, blocking biofilm formation, and disrupting morphological transition in C. albicans. NP256 enhances C. albicans susceptibility to some known antifungals significantly. The present study demonstrated the CaERG6 inhibitor NP256 as a potential class of antifungal compound for monotherapy or combinatory therapy.

Electrospray ionization tandem mass spectrometry of chaetoglobosins.

RATIONALE: Chaetoglobosins are a family of macrocyclic polyketide alkaloids. They possess many similar isomers and exhibit a wide range of biological activities. Thus, there is a need for reliable, fast, and low-cost analysis of this class of compounds. METHODS: A series of seven chaetoglobosins from Chaetomium globosum, including two types of isomers, were investigated using electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS) in both positive- and negative-ion mode. The identity of major product ions was supported by deuterium-labeling experiments. RESULTS: In positive-ion mode, the product ion at m/z 130 is the characteristic ion of the indolyl group. A McLafferty rearrangement might play a significant role in the fragmentation of the macrocycle moiety for most chaetoglobosins and produces two series of characteristic product ions, accompanied by neutral losses. The characteristic product ion at m/z 309 in the MS/MS spectrum of chaetoglobosins E indicates the structure of the cyclic olefinic bond in ring B and can be used to distinguish it from the isomers, chaetoglobosins F(ex) , which has an exocyclic double bond on ring B. In negative-ion mode, the McLafferty rearrangement has an important role in the fragmentation pattern of the macrocycle. Some high-abundance radical ions were detected. The radical product ion at m/z 138 might differentiate chaetoglobosins F and penochalasin F, isomers which have very similar structures. CONCLUSIONS: In summary, complementary information obtained from fragmentation experiments of [M+H](+) and [M-H](-) precursor ions is especially valuable for rapid identification of chaetoglobosins. The high-abundance radical ions in negative-ion mode are also of scientific interest.

Structural identification and UPLC-ESI-QTOF-MS2 analysis of flavonoids in the aquatic plant Landoltia punctata and their in vitro and in vivo antioxidant activities.

Duckweeds have long been consumed as vegetables in several South Asian countries. In this study of the chemical constituents of duckweed Landoltia punctata, a new compound, apigenin 6-C-[ß-D-apiofuranosyl-(1 â†’ 2)]-ß-D-glucopyranoside (1), and a previously LC-MS identified compound, quercetin 3-O-ß-D-apiofuranoside (3), as well as three known compounds, luteolin 6-C-[ß-D-apiofuranosyl-(1 â†’ 2)]-ß-D-glucopyranoside (2), apigenin 6-C-ß-D-glucopyranoside (4), and luteolin 7-O-neohespirodise (5), were isolated and identified on the basis of MS and NMR spectroscopic analyses and chemical derivations. In total, 24 flavonoids were identified in L. punctata 0001 by UPLC-ESI-QTOF-MS2. In DPPH and ABTS assays, 3 exhibited significant antioxidant activity with IC50 values of 4.03 ± 1.31 µg/mL and 14.9 ± 2.28 µg/mL, respectively. In in vivo antioxidant activity assays, 1 significantly increased the survival rate of juglone-exposed Caenorhabditis elegans by 2 to 3-fold, and by 75% following thermal damage. Compounds 1-5 exhibited moderate scavenging capacities of intracellular reactive oxygen species in C. elegans exposed to H2O2.

Analysis of sesterterpenoids from Aspergillus terreus using ESI-QTOF and ESI-IT.

INTRODUCTION: Biosynthesis of terretonin was studied due to the interesting skeleton of this series of sesterterpenoids. Very recently, López-Gresa reported two new sesterterpenoids (terretonins E and F) which are inhibitors of the mammalian mitochondrial respiratory chain. Mass spectrometry (MS), especially tandem mass spectrometry, has been one of the most important physicochemical methods for the identification of trace natural products due to it rapidity, sensitivity and low levels of sample consumption. The potential application prospect and unique skeleton prompted us to study structural characterisation using MS. OBJECTIVE: To obtain sufficient information for rapid structural elucidation of this class of compounds using MS. METHODOLOGY: The elemental composition of the product ions was confirmed by low-energy ESI-CID-QTOF-MS/MS analyses. The fragmentation pathways were postulated on the basis of ESI-QTOF-MS/MS/MS and ESI-IT-MS(n) spectra. Common features and major differences between ESI-QTOF-MS/MS and IT-MS(n) spectra were compared. For ESI-QTOF-MS/MS/MS experiments, capillary exit voltage was raised to induce in-source dissociation. Ammonium acetate or acetic acid were added into solutions to improve the intensity of [M + H]+. The collision energy was optimised to achieve sufficient fragmentation. Some fragmentation pathways were unambiguously proposed by the variety of abundance of fragment ions at different collision energies even without MS(n) spectra. RESULTS: Fragmentation pathways of five representative sesterterpenoids were elucidated using ESI-QTOF-MS/MS/MS and ESI-IT-MS(n) in both positive- and negative-ion mode. The key group of characterising fragmentation profiles was ring B, and these fragmentation patterns are helpful to identify different types of sestertepenoids. CONCLUSION: Complementary information obtained from fragmentation experiments of [M + H]+ (or [M + NH4]+ and [M-H](-) precursor ions is especially valuable for rapid identification of this kind of sesterterpenoid.

16-O-Methyl-cafestol.

THE TITLE COMPOUND [SYSTEMATIC NAME: (3bS,5aS,7R,8R,10aR,10bS)-7-meth-oxy-10b-methyl-3b,4,5,6,7,8,9,10,10a,10b,11,12-dodeca-hydro-5a,8-methano-5aH-cyclo-hepta-l[5,6]naph-tho[2,1-b]furan-7-methanol], C(21)H(30)O(3), was isolated from the beans of Coffea robusta. The mol-ecule contains five fused rings including a furan ring. The two six-membered rings are in chair conformations, but the third six-membered ring and the five-membered aliphatic ring adopt envelope conformations. Inter-molecular O-H⋯O hydrogen bonding is present in the crystal structure.

(3S,NR)-3-Hydroxy-methyl-2-methyl-2-(3-methyl-but-2-en-1-yl)-1,2,3,4-tetra-hydro-isoquinolinium bromide-1,1'-bi-2-naphthol (1/1).

In the title compound, C(16)H(24)NO(+)·Br(-)·C(20)H(14)O(2), the N-hetero-cyclic six-membered ring assumes a half-chair conformation. The two naphthalene ring systems are nearly perpendicular to one another, making a dihedral angle of 89.5 (2)°. Inter-molecular O-H⋯Br hydrogen bonding helps to stabilize the crystal structure.

ent-Kaurane and cembrane diterpenoids from Isodon sculponeatus and their cytotoxicity.

Nine new ent-kauranoids, sculponins D-L (1-9), and 14 known diterpenoids (10-23) were isolated from the aerial parts of Isodon sculponeatus. The structures of the new diterpenoids were determined by detailed interpretation of their 1D and 2D NMR spectra and HRESIMS. The isolated compounds were evaluated for their cytotoxic activities against a small panel of human cancer cell lines.

Azaphilone Alkaloids with Anti-inflammatory Activity from Fungus Penicillium sclerotiorum cib-411.

Nine new azaphilone alkaloids, penazaphilones A-I (1-9), were isolated from the solid fermented rice culture of Penicillium sclerotiorum cib-411. The structures of compounds 1-9 were elucidated based on HRESIMS, NMR, and CD spectroscopic data. The structures of 5 and 8 were confirmed by X-ray crystallographic analyses. Biological evaluation showed that compounds 1, 5, 6, and 8 inhibited the production of nitric oxide (NO) on RAW 264.7 cells stimulated by lipopolysaccharide with IC50 values of 15.29, 9.34, 9.50, and 7.05 µM, respectively. Meanwhile, they did not exhibit obvious cytotoxicity at a concentration of 50.0 µM.

Hydroxycinnamoylmalated flavone C-glycosides from Lemna japonica.

Three previously undescribed flavone C-glycosides (1-3), along with seven known ones (4-10), were isolated and characterized from the smallest flowering aquatic plant, Lemna japonica. On the basis of spectroscopic analysis and alkaline hydrolysis, compounds 1-3 were identified to be luteolin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (1), apigenin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (2), and luteolin 6-C-(2″-O-trans-coumaroyl-d-malate)-ß-glucoside (3). Compounds 1-3 are characteristic of a trans-coumaroyl-d-malate or trans-caffeoyl-d-malate linked to C-2″ of the glucose, which was reported for the first time. Compounds 1-3 exhibited weak cytotoxicity against HepG-2, SW-620, and A-549 cell lines, with IC50 values between 42.5 and 19.2µg/ml, and moderate antioxidant activity. Meanwhile compound 3 displayed moderate nematocidal activity with an EC50 value of 1.56mg/ml.

Xylastriasan A, a new cytochalasan from the fungus Xylaria striata.

Xylastriasan A (1), a new cytochalasan alkaloid with a rare 5/6/6/5/6 pentacyclic skeleton, and ergosterol (2) were isolated from the ethanol extract of fruiting bodies of the fungus Xylaria striata. Their structures were determined by analysis of their spectroscopic data. Compound 1 exhibited weak cytotoxic activity against HEPG2, B16 and A549 cell lines with IC50 values of 93.61, 85.61 and 91.58 µM, respectively. Ergosterol (2) potentiated pentobarbital-induced sleep by not only increasing the number of falling asleep and prolonging sleeping time but also reducing sleep latency at a dosage of 5 mg/kg.

Electrospray tandem mass spectrometry of epipolythiodioxopiperazines.

Low-energy collision-induced electrospray ionization tandem mass spectrometry ESI-CID-MS/MS (in the positive ion mode) was used for the structural characterization of a series of five representative epioplythiodioxopipreazines: dethiotetra(methylthio)chemotin, chaetocochins A, B and C, and chemotin isolated from the fungus Chaetomium cochliodes. The fragmentation pathways were elucidated by ESI-IT-MS(n). The elemental compositions of most of the product ions were confirmed by low-energy ESI-CID-QTOF-MS/MS analyses. The loss of the S(2) molecule seems always to be the first when the S--S bond is present. The loss of 77 Da corresponding to the loss of the [CH(3)SCH(2)O]' radical was diagnostic for chaetocochins A and B, in which the two piperazines rings are linked by an acetal group. It was found that a McLafferty rearrangement plays a significant role in the skeleton fragmentation of theses series of studied complex multicyclic piperazine compounds. This MacLafferty rearrangement affords the product ions at m/z 416 and 400, containing the two piperazine rings belonging to the epipolythiodioxopipreazines. In addition, the pentacyclic rearrangement involving the loss of the SMe(.) radical seems to occur in the presence of the unfused ring. Finally the product ions at m/z 635 and 591 seem to be the characteristic ions for chaetocochin A.

Chaetoindicins A-C, three isoquinoline alkaloids from the fungus Chaetomium indicum.

[structure: see text] Chaetoindicins A-C (1-3), three isoquinolines with novel skeletons, were isolated from the solid-state fermented culture of Chaetomiumindicum. Their structures were elucidated on the basis of spectral data. X-ray crystallographic analysis confirmed the structure of 2.

Cytotoxic ent-kauranoids from Isodon parvifolius.

Three new ent-kaurane diterpenoids, parvifoline Z (1), parvifoline AA (2), and parvifoline AB (3), together with 14 known compounds, were isolated from the leaves of Isodon parvifolius. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopy and mass spectrometry, and by comparison with known compounds. These three new diterpenoids included three types of ent-kauranoids, namely, C(20)-non-oxygenated-ent-kauranoid, 7,20-cyclo-ent-kauranoid and 6,7-seco-ent-kauranoid-7,20-olide. Compounds 1 and 2 exhibited significant cytotoxicities against A549, HT-29, and K562 cell lines.

A new alternariol glucoside from fungus Alternaria alternate cib-137.

A new secondary metabolite, 2-O-methylalternariol 4-O-ß-[4-methoxyl-glucopyranoside] (1), together with four known compounds alternariol methyl ether (2), altenuene (3), isoaltenuene (4) and 2-(2'S-hydroxypropyl)-5-methyl-7-hydroxychromone (5), was isolated from the fungus Alternaria alternate cib-137. Its structure was elucidated on the basis of spectroscopic data. Compounds 3 and 4 demonstrated moderate activity against Staphylococcus aureus.

Isochaetomium A2, a new bis(naphthodihydropyran-4-one) with antimicrobial and immunological activities from fungus Chaetomium microcephalum.

Isochaetomium A2 (1), a new bis(naphthodihydropyran-4-one), along with chaetochromins A (2) and B (3), was isolated from the solid-state fermented rice culture of Chaetomium microcephalum. The structure of compound 1 was elucidated on the basis of 1D and 2D NMR spectral data, and the relative configuration was confirmed by CD spectrum. Compounds 1-3 possessed significant antimicrobial activity against Escherichia coli 1.044, Staphylococcus aureus 1.252, and Bacillus subtilis 1.079. Moreover, compounds 1-3 showed obvious inhibitory effects on mouse spleen cell proliferation with successive IC50 values of 0.52, 0.19, and 0.24 µM.

A new chlorinated diphenyl ether and five known polyketide metabolites from Penicillium griseofulvum cib-119.

A series of polyketide metabolites (1-6), including a new chlorinated diphenyl ether (4-chloro-7,4'-dihydroxy-5,2'-dimethoxy-2-methylformate-6'-methybenzophone, 1), were isolated from the solid-fermented rice culture of Penicillium griseofulvum cib-119. The structure of compound 1 was determined on the basis of NMR spectra and single-crystal X-ray diffraction analyses. In addition, compound 1 showed weak cytotoxic activity against prostatic carcinoma cell (PC-3). Compounds 3-5 exhibited significant antimicrobial activities against Staphylococcus aureus and Bacillus subtilis.