Harzianic acids and oxazolidinone from the endophytic fungus Ilyonectria sp. and their cytotoxicity activity.

Four undescribed compounds including three harzianic acids (1, 3 and 4) and one oxazolidinone (2), along with three known ones (5-7) were isolated from the solid fermented product of endophytic fungus Ilyonectria sp., their structures were elucidated as 1-amino-harzianic acid (1), ilyonectria-oxazolidinone (2),10'-nor- isoharzianic acid (3), isohomoharzianic acid (4), harzianic acid (5), isoharzianic acid (6), homoharzianic acid (7) by means of detailed chemical evidences and spectroscopic data analysis. All the compounds were evaluated for cytotoxicity against SMMC-7721 human cancer cell lines by MTS assay. Among the seven tested compounds, 1-amino-harzianic acid (1) demonstrated well cytotoxic activity against SMMC-7721 with IC50 value of 26.84 µM. The results of molecular docking indicated that compound exhibited moderate anti-tumor activity may through binding to apoptosis related proteins.

Chromones from the endophytic fungus Bipolaris eleusines.

Eight previously undescribed chromones eleusineketones A-H (1-8), as well as eight known compounds (9-16), were isolated from the endophytic fungus Bipolaris eleusines. These planar structures were created using an in-depth analysis of their spectral data, which included 1D, 2D, and HRESIMS data. Furthermore, the absolute configurations of compounds 1, 2, and 6 were determined by spectroscopic analysis and quantum chemical computational approaches, and compound 5 was determined by single-crystal X-ray diffraction analysis. The cytotoxic activity assay revealed that compounds 1 and 5 both inhibited MDA-MB-231 cells with IC50 values of 14.48 µM and 17.99 µM, respectively.

The antifungal properties of terpenoids from the endophytic fungus Bipolaris eleusines.

A series of terpenoids (1-17), comprising six new compounds designated bipolariterpenes A-F (1-6) and eleven recognized compounds (7-17), were isolated from the wheat culture of the potato endophytic fungus Bipolaris eleusines. Their structures and stereochemistry were clarified by HRESIMS, NMR, DP4 + probability analyses, and computations for electronic circular dichroism (ECD). All compounds are made up of six meroterpenoids, four sesterterpenes and seven sesquiterpenes. Among them, four sesterterpenes (4, 5, 10, 11) were investigated for their antifungal, antibacterial and cytotoxic properties, and six meroterpenoids (1-3, 7-9) were evaluated for their antifungal properties. The compounds 7, 9, and 10 had substantial antifungal activity against Epidermophyton floccosum at a concentration of 100 µM. No antibacterial and cytotoxic activities were observed.

Boerelasins A-D, Four Unprecedented Cytochalasins from the Endophytic Fungus Boeremia Exigua.

Four undescribed cytochalasins (1-4) were isolated from the endophytic fungus Boeremia exigua. Structurally, boerelasin A (1) represents the first example of a cytochalasin with a rare 5/5 bicyclic carbon core. Boerelasin B (2) possesses an unprecedented 5/6/5/6/8 pentacyclic ring system. Boerelasin C (3), a derivative from the common biosynthetic intermediate to 1, is a macrocyclic ring-opening cytochalasin, and boerelasin D (4) contains an uncommon six-carbon alkyl acid side chain. The structures were elucidated based on spectroscopic methods, electronic circular dichroism, spin-spin coupling constants, and calculated nuclear magnetic resonance with DP4+ analysis. These compounds exhibited significant cytotoxicity against the tumor cells.

Pimarane Diterpenes from Fungi.

Pimarane diterpenes are a kind of tricyclic diterpene, generally isolated from plant and fungi. In nature, fungi distribute widely and there are nearly two to three million species. They provide many secondary metabolites, including pimarane diterpenes, with novel skeletons and bioactivities. These natural products from fungi have the potential to be developed into clinical medicines. Herein, the structures and bioactivities of 197 pimarane diterpenes are summarized and the biosynthesis and pharmacological researches of pimarane diterpenes are introduced. This review may be useful improving the understanding of pimarane diterpenes from fungi.

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).

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.

Ophiorrhines F and G, Key Biogenetic Intermediates of Ophiorrhine Alkaloids from Ophiorrhiza japonica and Their Immunosuppressant Activities.

Continued interest in bioactive alkaloids led to the isolation of two undescribed alkaloids, ophiorrhines F (1) and G (2), from the aerial parts of Ophiorrhiza japonica. Their structures were elucidated based on spectroscopic methods, electronic circular dichroism, and calculated NMR with DP4+ analysis. These two alkaloids represent key biological genetic intermediates in the formation of ring C in the ophiorrhines. Compound 1 exhibited good inhibition on LPS-induced B cell proliferation with an IC50 value of 0.38 µM and showed significant selective inhibitory activity on a B cell proliferation response with a selective index of 548.42. A preliminary study indicated that 1 may have a new mechanism of immunosuppression.

Oblongolides from endophytic fungus Phoma bellidis Neerg. harbored in Tricyrtis maculata (D. Don) J.F.Macbr.

Five previously undescribed oblongolides, namely phomaones A-E, along with four known compounds, were isolated from the endophytic fungus Phoma bellidis Neerg.. Their structures and absolute configurations were determined by extensive experimental spectroscopic methods as well as single crystal X-ray diffractions, ECD calculations and GIAO 13C NMR calculations. Phomaone A represent the first example of oblongolides with glycol directly linked by two C-C bonds, and its biosynthetic pathway were proposed. The cytotoxicity of obtained compounds was evaluated against human cancer cell lines MCF-7, DU145, and SW480. All compounds except phomaone A showed the cytotoxicity against MCF-7 with IC50 value ranging from 12.45 to 49.84 µM.

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.

Identification and Bioactivities of Secondary Metabolites Derived from Endophytic Fungi Isolated from Ethnomedicinal Plants of Tujia in Hubei Province: A Review.

Tujia is a national minority, inhabiting in the mountainous Wuling area in China. Since 1978, Tujia medicine has been studied, summarized and developed, leading to numerous achievements by Chinese researchers, such as the publishing of approximately 30 monographs of Tujia medicine. These publications are focused on summarizing and improving the theory of Tujia medicine and developing clinical therapies from this system of medicine. The shortage of natural medicinal plants used in Tujia medicine has created the need to discover new resources to replace them and protect endangered natural plant species. Endophytic fungi are one of the conservation options, are considered a source of new bioactive natural products, and are a renewable and inexhaustible source of new drugs and agrochemicals. This review summarizes 260 compounds from endophytic fungi that have been previously isolated from the medicinal plants of Tujia. These compounds include steroids, terpenoids, meroterpenoids, polyketides, alkaloids, peptides, aliphatic compounds, aromatic compounds, and heterocyclic compounds.

Immunosuppressive Isopimarane Diterpenes From Cultures of the Endophytic Fungus Ilyonectria robusta.

Five new isopimarane diterpenes, robustaditerpene A-E (1-5), which include 19-nor-isopimarane skeleton and isopimarane skeleton, were isolated from the liquid fermentation of the endophytic fungus Ilyonectria robusta collected from Bletilla striata. The structure elucidation and relative configuration assignments of all compounds were accomplished by interpretation of NMR and HRESIMS spectrometric analyses and 13C NMR calculation. And the absolute configuration of 1-5 were identified by single-crystal X-ray diffraction and ECD calculation. Compound 3 inhibited lipopolysaccharide-induced B lymphocytes cell proliferation with an IC50 value at 17.42 ± 1.57 µM while compound 5 inhibited concanavalin A-induced T lymphocytes cell proliferation with an IC50 value at 75.22 ± 6.10 µM. These data suggested that compounds 3 and 5 may possess potential immunosuppressive prospect.

Characterization of the complete chloroplast genome of a well-known Chinese medicinal herb, Scrophularia ningpoensis.

Scrophularia ningpoensis has been used as a famous traditional medicinal herb in Asian countries to treat jaundice, dysentery, and the pain of rheumatism. In this paper, the complete chloroplast (cp) genome sequence of S. ningpoensis was reported and characterized. The cp genome is 153,175 bp in length, composed of a pair of 25,490 bp inverted repeat (IR) regions separated by a large single copy (LSC) region of 84,257 bp and a small single copy (SSC) region of 17,938 bp. There were 130 predicted genes (85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes) in the genome, and the overall GC content of the genome is 38%. Phylogenetic analysis based on the cp genome data showed that S. ningpoensis was sister to S. buergeriana.

Trichothecrotocins D-L, Antifungal Agents from a Potato-Associated Trichothecium crotocinigenum.

Seven new merosesquiterpenoids, trichothecrotocins D-J (1-7), two new trichothecene sesquiterpenoids, trichothecrotocins K (12) and L (13), and six known compounds (8-11, 14, and 15), were isolated from a potato-associated fungus, Trichothecium crotocinigenum. Compounds 5 and 6 were racemates which were further separated as pure enantiomers. Structures together with absolute configurations were established by extensive spectroscopic analysis, as well as quantum chemistry calculations on ECD and optical rotations. Compounds 1-4 are rare meroterpenoids featuring a seco-phenyl group, while 1 and 2 possessed a novel 6-6/5 fused ring system. Compounds 1-4, 8, 11, and 12 showed antifungal activity against four plant pathogens with MIC values of 8-128 µg/mL. It is suggested that the meroterpenoids produced by T. crotocinigenum may play an important role in the antifungal property of the fungus, thereby protecting the host plant, i.e., potato.

Depsidones and diaryl ethers from potato endophytic fungus Boeremia exigua.

Three depsidones boremexins A-C (1-3), two diaryl ethers boremexins D (4) and E (5), together with four known compounds were obtained from cultures of potato endophytic fungus Boeremia exigua. Their structures with absolute configurations were established by extensive spectroscopic methods and electronic circular dichroism (ECD) calculations. Compounds 1-4, 6, and 9 displayed anti-inflammatory properties on nitric oxide production in LPS-induced RAW264.7 macrophages with an IC50 range of 19.4-34.4 µM. Compounds 2 and 5 exhibited cytotoxicities to human breast cancer cell line (MCF-7) with IC50 values of 33.1 and 4.0 µM, respectively.

Novel Metabolites from the Endophytic Fungus Chaetomium subaffine L01.

One natural p-terphenyl glycoside, gliocladinin C, and two furano-polyene derivatives, chaetominins A and B, were isolated from potato endophytic fungus Chaetomium subaffine. The absolute configurations of these compounds were elucidated by HR-ESI-MS, NMR, the DP4+ probabilities and electronic circular dichroism (ECD) spectra. Furthermore, gliocladinin C and chaetominin A showed cytotoxic activity against two selected human tumor cell lines (Hep-2 and HepG-2).

Xylarichalasin A, a Halogenated Hexacyclic Cytochalasan from the Fungus Xylaria cf. curta.

A cytochalasan, xylarichalasin A, was obtained from the endophytic fungus Xylaria cf. curta harbored in Solanum tuberosum. Its structure was elucidated by comprehensive spectroscopic methods including HRESIMS, 1D/2D NMR, and residual dipolar coupling analysis as well as quantum chemistry calculations including DFT GIAO 13C NMR and ECD calculation. It has an unprecedented 6/7/5/6/6/6 fused polycyclic structure. In bioassay, xylarichalasin A showed cytotoxicity against human cancer cell lines with IC50 value ranging from 6.3-17.3 µM.

Curtachalasins, immunosuppressive agents from the endophytic fungus Xylaria cf. curta.

Eleven new cytochalasins, curtachalasins F-P (1-11), were isolated from the rice fermentation of endophytic fungus Xylaria cf. curta. Their structures were identified by extensive spectroscopic methods, X-ray diffraction, and quantum chemistry calculations. Curtachalasin P possesses a unique 5/6/6/7 fused ring system. In the bioactivity screening for curtachalasins F-P, A-C, and E (1-15), compounds 1, 3-6, 8-13, and 15 did not show obvious cytotoxicity against primary mouse splenocytes. Furthermore, the immunosuppressive assay against concanavalin A (ConA) induced T lymphocyte cell proliferation and lipopolysaccharide (LPS) induced B lymphocyte cell proliferation showed that compound 1 results in significant selective inhibition on B-cell proliferation (IC50 value of 2.42 µM) and compound 10 has selective inhibition on T-cell proliferation (IC50 value of 12.15 µM). These interesting immunosuppressive properties of this class of compounds provide new clues to fulfill the urgent demand for new immunosuppressive drugs.

Cytotoxic 19,20-epoxycytochalasans from endophytic fungus Xylaria cf. curta.

Nine new 19,20-epoxycytochalasans (1-9) were isolated from the rice fermentation extracts of endophytic fungus Xylaria cf. curta, along with four known compounds 19,20-epoxycytochalasin C (10), 18-desoxy-19,20-epoxycytochalasin C (11), 19,20-epoxycytochalasin D (12) and 5,6-dihydro-7-oxo-19,20-epoxycytochalasin C (13). Their structures and absolute configurations were determined by 1D and 2D NMR, HRESIMS, X-ray diffraction and ECD calculation. The cytotoxicity of obtained compounds (1-13) was evaluated against human cancer cell lines HL-60, A549, SMMC-7721, MCF-7, and SW480. Remarkably, compound 10 showed significant specific cytotoxicity against HL-60 cell lines with IC50 value of 1.11 µM.