Glucoconjugated monoterpene indole alkaloids with xanthine oxidase inhibitory activity from Ophiorrhiza japonica.

Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1-5), ophiorglucidines A-E, and seven known analogues (6-12) from the water-soluble fraction of Ophiorrhiza japonica. The structures were elucidated based on spectroscopic data and quantum calculations as well as X-ray crystallographic analysis. The structure of 1 was characterized as a hexacyclic skeleton including a double bridge linking the indole and the monoterpene moieties, which is the first report of a single crystal with this type of structure. Moreover, the inhibitory effect of zwitterionic indole alkaloid glycosides on xanthine oxidase was found for the first time. The alkaloids 2 and 3, both of which have a pentacyclic zwitterionic system, were more active than the reference inhibitor, allopurinol (IC50 = 11.1 µM) with IC50 values of 1.0 µM, and 2.5 µM, respectively. Structure-activity relationships analyses confirmed that the carbonyl group at C-14 was a key functional group responsible for the inhibitory effects of these alkaloids.

Triquinane Sesquiterpene Glycosides from the Basidiomycete Antrodiella zonata.

In our ongoing study of fungal bioactive natural products, 12 previously undescribed triquinane sesquiterpene glycosides, namely, antrodizonatins A-L (1-12), and four known compounds (13-16) have been obtained from the fermentation of the basidiomycete Antrodiella zonata. The structures were established unambiguously via extensive spectroscopic analysis and theoretical calculations of electronic circular dichroism spectra. This is the first report of triquinane sesquiterpene glycosides. Compounds 1, 5, and 12 displayed antibacterial activity against Staphylococcus aureus with MIC50 values of 35, 34, and 69 µM, respectively.

Antibacterial Metabolites from Kiwi Endophytic Fungus Fusarium tricinctum, a Potential Biocontrol Strain for Kiwi Canker Disease.

Pseudomonas syringae pv. actinidiae (Psa) is a Gram-negative bacterium causing the kiwifruit canker disease, resulting in serious economic losses to the kiwifruit industry. This study investigated the use of an endophytic fungus, Fusarium tricinctum, obtained from the kiwi plant (Actinidia chinesis) as a potential biocontrol strain against the Psa. F. tricinctum showed an inhibition rate of 59.5% in vitro against Psa. Bioassay-guided isolation was conducted on the cultural broth of F. tricinctum and seven new imidazole alkaloids, (±)-fusaritricine J ((±)-1) and fusaritricines K-P (2-7), and four enniatins (8-11) were identified. Their absolute configurations were established through extensive spectroscopic methods, quantum chemical calculations, and X-ray single crystal diffraction. Compounds 1, 4, 5, and 8-11 showed comparable anti-bacterial activities against Psa as positive control, with MIC values of 25-50 µg/mL. Further cell membrane permeability assay suggested that the most active compound 4 could destroy the bacterial cell wall structure. Hence, F. tricinctum metabolites could be applied as potential anti-Psa agents, and F. tricinctum could be considered a biocontrol strain for the control of the kiwifruit canker disease.

Nine New Pregnane Glycosides from the Cultivated Medicinal Plant Marsdenia tenacissima.

The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I (1-9), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the Rf values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A (1) featured an unusual 8,14-seco-pregnane skeleton. Compounds 1, 8, and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC50 values of 37.5, 38.8, and 42.8 µM (L-NMMA was used as a positive control, IC50 39.3 µM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.

Three new oxygenated yohimbane-type alkaloids from Ophiorrhiza japonica.

A series of oxygenated yohimbane alkaloids, including three new compounds, ophiorrhines H-J (1-3), and seven known compounds, were isolated from the aerial parts of Ophiorrhiza japonica. The structures with absolute configurations were elucidated by extensive MS and NMR spectroscopic methods, as well as the single crystal X-ray diffraction and ECD calculations. Ophiorrhines H (1) and I (2) represent key oxygenated intermediates in the formation of aromatic ring E in the demethoxycarbonyl-3,14-dihydrogambirtannine (10). Ophiorrhine J (3) is a highly oxidized yohimbane derivative with the planar superconjugated system. The cytotoxic activities of all alkaloids against five human cancer cell lines were evaluated.

A new dimeric (-)-5-methylmellein from cultures of the basidiomycete Inonotus sinensis.

(-)-5-Methylmellein (1) and its new dimer (2) were isolated from cultures of the basidiomycete Inonotus sinensis. Their structures were elucidated on the basis of extensive spectroscopic methods including UV, IR, HR-EI-MS, 1D NMR and 2D NMR. The structure of Compound 2 was determined by single-crystal X-ray crystallographic analysis. Compound 2 was tested for the cytotoxicities against five human cancer cell lines.

α-Glucosidase inhibitory phenylpropanoid-dihydrochalcone hybrids from the leaves of medicinal plant Malus hupehensis (Pamp.) Rehder.

Eight undescribed phenylpropanoid-dihydrochalcone hybrids, namely (+)- and (-)-malahupin A, (+)- and (-)-malahupin B, (±)-malahupin C, malahupinosides A and B, 7‴-epi-malahupinoside B, together with two known compounds, phloretin and phlorizin, were isolated from the leaves of the folk medicinal plant Malus hupehensis. Their structures were elucidated by extensive NMR and MS spectroscopic methods, chiral-phase analysis, and ECD calculations. Compounds (+)-malahupin B and malahupinoside B showed weak inhibition activities against the nitric oxide production in liposaccharide-induced murine RAW264.7 macrophages with IC50 values of 36.7 and 27.0 µM, respectively. Compounds (+)- and (-)-malahupin A, (+)- and (-)-malahupin B exhibited significant α-glucosidase inhibitory activity, with IC50 values of 22.5, 19.1, 19.2, and 17.4 µM, respectively. The postulated biosynthetic pathways to these hybrid compounds were proposed. This work represents the first report of the natural phenylpropanoid-dihydrochalcone hybrid compound, and lays foundation for the study on the bioactive principles of the ethnic hypoglycemic medicinal plant.

Paecilins F-P, new dimeric chromanones isolated from the endophytic fungus Xylaria curta E10, and structural revision of paecilin A.

A total of eleven new dimeric chromanones, paecilins F-P (2-12), were isolated from the endophytic fungus Xylaria curta E10, along with four known analogs (1, 13-15). Their structures and absolute configurations were determined by extensive experimental spectroscopic methods, single-crystal X-ray diffraction, and equivalent circulating density (ECD) calculations. In addition, the structure of paecilin A, which was reported to be a symmetric C8-C8' dimeric pattern, was revised by analysis of the nuclear magnetic resonance (NMR) data, and single-crystal X-ray diffraction. Compound 1 showed antifungal activity against the human pathogenic fungus Candida albicans with a minimum inhibitory concentration of 16 µg/mL, and Compounds 8 and 10 showed antibacterial activity against the gram-negative bacterium Escherichia coli with the same minimum inhibitory concentration of 16 µg/mL.

Four New Highly Oxygenated Eremophilane Sesquiterpenes from an Endophytic Fungus Boeremia exigua Isolated from Fritillaria hupehensis.

Four new eremophilane-type sesquiterpenes, boeremialanes A-D (1-4) were obtained from solid substrate cultures of Boeremia exigua (Didymellaceae), an endophytic fungus isolated from Fritillaria hupehensis (Liliaceae). Boeremialanes A-C (1-3) are highly oxygenated eremophilanes with a benzoate unit attached at the C-13 position and are rarely found in nature. Their structures and absolute configurations were determined by extensive spectroscopic methods, electronic circular dichroism (ECD), and nuclear magnetic resonance (NMR) calculations with DP4+ analysis. Boeremialane D (4) potently inhibited nitric oxide production in lipopolysaccharide-treated RAW264.7 macrophages with an IC50 of 8.62 µM and was more potent than the positive control, pyrrolidinedithiocarbamate (IC50 = 23.1 µM).

[20(22)E]-Lanostane Triterpenes from the Fungus Ganoderma australe.

Twelve new lanostane triterpenoids (1-5, 7-13) were isolated from the fruiting bodies of the fungus Ganoderma australe. The structures of the new compounds were elucidated by extensive 1D and 2D NMR, and HRESIMS spectroscopic analysis. All the triterpenes are featured by 20(22)E configurations which are uncommon in the Ganoderma triterpene family. The absolute configuration of the C-25 of compounds 1, 2, and 6 were determined by the phenylglycine methyl ester (PGME) method. A postulated biosynthetic pathway for compound 1 was discussed. This study opens new insights into the secondary metabolites of the chemically underinvestigated fungus G. australe.

Three new pyrrole alkaloids from the endophytic fungus Albifimbria viridis.

Three new pyrrole alkaloids albifipyrrols A-C (1-3), were isolated from the endophytic fungus Albifimbria viridis collected from the Chinese medicinal plant. Their structures were elucidated by extensive NMR and HRESIMS spectrometric analyses. All compounds were evaluated for immunosuppressive activity. Fortunately, compound 2 exhibits certain inhibition specifically against the LPS-induced proliferation of B lymphocyte cells with IC50 value 16.16 µM.

Cadinane sesquiterpenoids from the fungus Antrodiella albocinnamomea and their inhibitory activity against nitric oxide production.

Seven previously undescribed cadinane sesquiterpenoids, albocinnamins A‒G, were isolated from the fungus Antrodiella albocinnamomea. Their structures with absolute configurations were elucidated on the basis of extensive spectroscopic methods, as well as single crystal X-ray diffraction. Cadinane sesquiterpenoids were reported from A. albocinnamomea for the first time. All of these sesquiterpenoids possess an unusual ether ring with minor modifications. Albocinnamins D and G showed certain inhibitory activities against nitric oxide production in LPS-activated RAW264.7 macrophages with IC50 values of 26.1 and 19.2 µM, respectively.

Two new pyridine derivatives and two new furan derivatives from Irpex lacteus.

Two undescribed disubstituted pyridine derivatives irpexidines A and B (1 and 2) and two undescribed alkylfuran derivatives irpexins K and L (3 and 4) were isolated from fermentation broth of Irpex lacteus. Their structures were established by extensive spectroscopic methods. The pyridine derivatives from this fungus were reported for the first time. The new compounds were evaluated for their cytotoxicity against Hela cancer cell and inhibitory activity on NO production.

Immunosuppressive Sesquiterpenoids from the Edible Mushroom Craterellus odoratus.

The aim of this work was to comprehensively understand the chemical constituents of the edible mushroom Craterellus ordoratus and their bioactivity. A chemical investigation on this mushroom led to the isolation of 23 sesquiterpenoids including eighteen previously undescribed bergamotane sesquiterpenes, craterodoratins A-R (1-18), and one new victoxinine derivative, craterodoratin S (19). The new structures were elucidated by detailed interpretation of spectrometric data, theoretical nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculations, and single-crystal X-ray crystallographic analysis. Compounds 1 and 2 possess a ring-rearranged carbon skeleton. Compounds 3, 10, 12-15, 19, 20 and 23 exhibit potent inhibitory activity against the lipopolysaccharide (LPS)-induced proliferation of B lymphocyte cells with the IC50 values ranging from 0.67 to 22.68 µM. Compounds 17 and 20 inhibit the concanavalin A (ConA)-induced proliferation of T lymphocyte cell with IC50 values of 31.50 and 0.98 µM, respectively. It is suggested that C. ordoratus is a good source for bergamotane sesquiterpenoids, and their immunosuppressive activity was reported for the first time. This research is conducive to the further development and utilization of C. ordoratus.

Pardinumones A-D: Antibacterial Polyketide-Amino Acid Derivatives from the Mushroom Tricholoma pardinum.

Four polyketide-amino acid derivatives, pardinumones A-D (1-4), were isolated from the wild mushroom Tricholoma pardinum. Their structures together with absolute configurations were characterized by means of spectroscopic data analyses, as well as calculated electronic circular dichroism (ECD) and NMR with sorted training set (STS) protocol analysis. Compounds 1-4 exhibited antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli with MIC values in the range of 6.25-50 µg/mL.

Zopfiellasins A-D, Two Pairs of Epimeric Cytochalasins from Kiwi-Associated Fungus Zopfiella sp. and Their Antibacterial Assessment.

In our continuous search for antibacterial agents against Pseudomonas syringae pv. actinidiae (Psa) from kiwi-associated fungi, two pairs of epimeric cytochalasins, zopfiellasins A-D (1-4), were characterized from the fungus Zopfiella sp. The structures were established on the basis of spectroscopic data analysis, while the absolute configurations were determined by single-crystal X-ray diffraction. Compounds 1 and 3 exhibited antibacterial activity against Psa with MIC values of 25 and 50 µg/mL, respectively. This is the first report of anti-Psa activity of cytochalasin derivatives.

Taccachatrones A-G, Highly Oxidized Steroids from the Rhizomes of Tacca chantrierii and Their Cytotoxicity Assessment.

Seven highly oxidized steroids, taccachatrones A-G (1-7), together with four known taccalonolides (8-11), were characterized from the rhizomes of Tacca chantrieri. The structures of 1-7 were established on the basis of spectroscopic data analysis, while the absolute configurations were determined by single-crystal X-ray diffraction. Compounds 1-4 may be derived from taccalonolide derivatives by the degradation of three carbon atoms. Compounds 7, 8, 10, and 11 exhibited cytotoxicity to human cancer cell lines, indicating that the presence of a lactone moiety, as well as a double bond between C-22 and C-23, might play key roles in mediating their cytotoxicity.

Psathyrellins A-E, Antibacterial Guanacastane Diterpenoids from Mushroom Psathyrella candolleana.

Five previously undescribed guanacastane diterpenoids, namely psathyrellins A-E (1-5), were obtained from cultures of the mushroom Psathyrella candolleana. Their structures with absolute configurations were elucidated by extensive spectroscopic methods. Compounds 1-3 showed antibacterial activity against four strains with MIC values in a range of 16-128 µg/mL.

Structure and cytotoxicity of trichothecenes produced by the potato-associated fungus Trichothecium crotocinigenum.

Seven previously undescribed trichothecenes, named trichothecrotocins M-S (1-7), along with five known compounds, were isolated from rice cultures of the potato-associated fungus Trichothecium crotocinigenum. Their structures and absolute configurations were determined through spectroscopic methods, single-crystal X-ray diffraction, and quantum chemistry calculations on ECD. Compound 1 possesses a rare 6,11-epoxy moiety in the trichothecene family. Compound 6 exhibited strong cytotoxic activity against MCF-7 cancer cell lines with an IC50 value of 2.34 ± 0.45 µM. It promoted apoptosis induction in MCF-7 cells. Moreover, cell cycle analysis showed cell cycle arrest caused by compound 6 at the G2/M phase which resulted to cell proliferation inhibition and pro-apoptotic activity. Further quantitative real-time PCR (qRT-PCR) analysis confirmed that the G2/M arrest was accompanied by upregulation of p21 and down regulation of cyclins B1 in 6-treated MCF-7 cells.

Structures, Chemical Conversions, and Cytotoxicity of Tricholopardins C and D, Two Tricholoma Triterpenoids from the Wild Mushroom Tricholoma pardinum.

Two undescribed Tricholoma triterpenoids, namely tricholopardins C (1) and D (2), were isolated from the wild mushroom Tricholoma pardinum. Their structures with absolute configurations were elucidated by spectroscopic methods, as well as the single crystal X-ray diffraction. Compounds 1 and 2 were further obtained by chemical conversions from the known analogues. Compound 1 showed significant cytotoxicity to MCF-7 and Hela cell lines with IC50 values of 4.7 µM and 9.7 µM, respectively. Its mechanism of inducing MCF-7 cell apoptosis was studied briefly.