Asperustins A-J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856.

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.

Lignans and [11]-chaetoglobosins from Pseudeurotium bakeri and their immunosuppressive activity.

Two previously unreported lignans (1-2) and four undescribed [11]-chaetoglobosins (3-6) were obtained from the culture extract of an endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were determined by spectroscopic data analysis, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, the modified Mosher's method, and Mo2(OAc)4-induced electronic circular dichroism (ICD) experiments. Compounds 5 and 6 showed moderate cytotoxic effects against seven human cancer cell lines. Compounds 2-4 exhibited immunosuppressive activities on concanavalin A-induced T cell proliferation with IC50 values of 3.7, 3.4, and 14.5 µM, and on lipopolysaccharide-induced B cell proliferation with IC50 values of 4.1, 3.9, and 14.2 µM, respectively. Further investigation revealed that 2 and 3 induced apoptosis in activated T cells in a dose-dependent manner.

Chaepseubakerins A-J, ten undescribed cytotoxic [11]-chaetoglobosins from an endophytic fungus Pseudeurotium bakeri.

Ten previously unreported [11]-chaetoglobosins, chaepseubakerins A-J (1-10), were characterized from the solid rice-based culture of Pseudeurotium bakeri P1-1-1, an endophyte harbored in the roots of Macrocoma tenue subsp. sullivantii Vitt. (Orthotrichaceae). Their structures were determined by spectroscopic analysis, single-crystal X-ray diffraction (Cu Kα radiation), and chemical methods. Chaepseubakerin A (1) exhibited significant cytotoxic effects against seven human cancer cell lines, A549, A427, HCT116, HT-29, HeLa, HepG2, and MCF-7, with IC50 values of 2.9, 3.0, 4.0, 4.4, 7.1, 6.7, and 8.9 µM, respectively. Mechanistically, 1 induced G2/M cell cycle arrest and apoptosis in A549, Hela, and HCT116 cells in a dose dependent manner.

Isomeric eremophilane lactones from the whole plant of Parasenecio albus and their cytotoxic and immunosuppressive activities.

Ten previously unreported eremophilane lactones (parasalbolides A-J), including three pairs of C-10 epimers (parasalbolides A and G, B and H, and F and I, respectively), were isolated and identified from the whole plant of Parasenecio albus. Their structures were established on the basis of the HRESIMS and NMR spectroscopic analyses, combined with the comparison of the ECD spectra. The absolute configuration of parasalbolide A was confirmed by single-crystal X-ray diffraction using Cu Kα radiation. Parasalbolides A-J represent the first examples of 1,2,10-trioxygenated eremophila-7(11),8-dien-12,8-olides. The cytotoxic and immunosuppressive activities of selected isolates were evaluated and the (10S)-eremophilane lactones (parasalbolides A, B, and F) showed more potent activities than the (10R)-ones (parasalbolides G, H, and I).

2-Methoxyjuglone, a Promising Bioactive Compound for Pharmaceutical and Agricultural Purposes: A Review.

2-Methoxyjuglone, a member of the 1,4-naphthoquinone family, was first obtained through semi-synthesis based on 2-hydroxyjuglone as the precursor in 1966. It has been isolated and identified from different plant species of the Juglandaceae, Sterculiaceae, and Proteaceae families. 2-Methoxyjuglone has been demonstrated to possess a wide range of biological activities, including antitumor, antifungal, and antibacterial activities; in addition, it has been shown to poison fish and inhibit seed germination. These properties make 2-methoxyjuglone a promising bioactive compound for pharmaceutical and agricultural purposes. This review article provides an overview of the current research progress on 2-methoxyjuglone for the first time, with a primary focus on the plant sources, extraction, identification, synthesis, and biological activities associated with this compound for further development.

[11]-chaetoglobosins with cytotoxic activities from Pseudeurotium bakeri.

Fourteen new [11]-chaetoglobosins (1-14), along with two known congeners, cytochalasins X and Y (15 and 16), were isolated from the cultures of an endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures incorporating absolute configurations were elucidated based on the comprehensive analyses of one- and two-dimensional NMR data, HRESIMS spectrometry, chemical methods, and single-crystal X-ray diffraction analysis (Cu Kα). All isolates were evaluated for their cytotoxic activities and chaetopseudeurin M (1) displayed significant cytotoxic effects against seven human cancer cell lines, with IC50 values ranging from 5.1 ± 0.9 to 10.8 ± 0.1 µM. Western blot experiments exhibited that compound 1 exerted its cytotoxic effect in MCF-7 cells by inducing G2/M cell cycle arrest and apoptosis via downregulating the expression of cyclin B1 and Cdk1, and activating Bcl-2/caspase-3/PARP pathway, respectively.

TRAIL-sensitizing Cytochalasins from the Endophytic Fungus Phoma multirostrata.

Seven undescribed cytochalasins, multirostratins K - Q (2: -8: ), together with one known analogue, cytochalasin Z3 (1: ), were isolated from the culture of Phoma multirostrata XJ-2-1, an endophytic fungus obtained from the root of Parasenecio albus. Their structures with absolute configurations were determined by 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), electronic circular dichroism (ECD), single-crystal X-ray crystallography, and chemical methods. The structure of ascochalasin was revised from Δ 13 to Δ 21 by detailed analysis of the NMR data and by comparison with the data for 7: . In a TRAIL (tumor necrosis factor related apoptosis inducing ligand)-resistance-overcoming experiment, co-treatment of 2: or 6: with TRAIL reduced the cell viability of A549 cells by 30.3% and 27.5% at 10 µM, respectively.

Cytochalasan Alkaloids as TRAIL Sensitizers from an Endophytic Fungus Chaetomium sp.

Two new cytochalasans with a rare 6/6/5/5/7 pentacyclic ring system, named chaetoconvosins C-D (1: -2: ), together with two known congeners (3: -4: ), were isolated from the fermentation of an endophytic fungus, Chaetomium sp. SG-01, harbored in the fibrous roots of Schisandra glaucescens Diels. Their structures including the absolute configuration were elucidated by extensive spectroscopic (HRESIMS, NMR, and ECD) and X-ray crystallographic analyses. The TRAIL-resistance-overcoming activity of 1: -4: in a TRAIL-resistant HT29 colorectal cancer cell line was evaluated, which revealed that co-treatment of 1: -4: at 50 µM with TRAIL (150 ng/mL) reduced the HT29 cell viability by 19.0%, 24.1%, 17.9%, and 15.5%, respectively, compared to treatment with 1: -4: alone.

Chlorinated bisabolene sesquiterpenoids from the whole plant of Parasenecio rubescens.

Four new chlorinated bisabolene-type sesquiterpenoids (1-4) were isolated during the phytochemical investigation of an acetone extract of the whole plant of Parasenecio rubescens. The structures of 1-4 were determined by analysis of their HRESIMS and NMR spectroscopic data, and the absolute configuration of 1 was established through single-crystal X-ray diffraction. All isolates were evaluated for their cytotoxicity against three cancer cell lines (B16 mouse melanoma, HepG2 human hepatocellular carcinoma, and MCF7 human breast adenocarcinoma), as well as their antimicrobial effects against Staphylococcus aureus, Escherichia coli, and Monilia albicans. As a result, compounds 1-4 displayed a certain degree of antimicrobial activities.

Resorcylic acid lactones from a Podospora sp. that induce apoptosis in activated T cells through MAPKs/AKT pathway.

Podomycins A-L (1-12), 12 undescribed hypothemycin-type resorcylic acid lactones (RALs), were characterized from Podospora sp. G214, an endophyte harbored in the roots of Sanguisorba officinalis L. Their structures were addressed by spectroscopic data, X-ray crystallography, the modified Mosher's method, together with Mo2(OAc)4- and Rh2(OCOCF3)4-induced electronic circular dichroism (ICD) experiments. Podomycins A-C (1-3) represent the first class of natural RALs with a 13-membered macrolactone ring, while 4-12 are rearranged methoxycarbonyl substituted RALs. Biologically, compounds 2, 6, 8, 10, and 12 displayed immunosuppressive activities against T cell proliferation with IC50 values of 14.5-21.9 µM, and B cell proliferation with IC50 values of 22.3-36.5 µM, respectively. Further mechanism of action research demonstrated that podomycin F (6) distinctly induced apoptosis in activated T cells via MAPKs/AKT pathway.

[11]-Chaetoglobosins from Pseudeurotium bakeri Induce G2/M Cell Cycle Arrest and Apoptosis in Human Cancer Cells.

Twelve new [11]-chaetoglobosins, chaetopseudeurins A-L (1-12), were identified from the fermentation of the endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Compounds 2 and 5-7 exhibited significant cytotoxicities against seven human cancer cell lines, with IC50 values ranging from 4.7 ± 1.0 to 12.2 ± 0.7 µM, and induced G2/M cell cycle arrest and apoptosis in MCF-7 and A427 cells dose dependently. Western blot analysis showed that compound 2 induced apoptosis of MCF-7 cells via the Bcl-2/caspase-3/PARP pathway.

Phenolic constituents from the fresh pericarps of Juglans sigillata.

Three new phenolic compounds, 2,3,4-trihydroxy-1-(4'-hydroxybenzyl)benzoic acid (1), 2,3,4-trihydroxy-1-(4'-hydroxy-3'-methoxybenzyl)benzoic acid (2), and 2-(4'-hydroxy-3'-methoxybenzyl)-3,5-dimethoxy-1,4-benzoquinone (3), were isolated from the fresh pericarps of Juglans sigillata Dode. Their structures were elucidated by integrated spectroscopic techniques. Bioactivity screening results showed that compounds 1-3 exhibited moderate neuroprotective effects against H2O2-induced or CoCl2-induced cellular damage in human neuroblastoma SH-SY5Y cell line.

Triterpenoids from the fresh pericarps of Juglans hopeiensis.

Two new triterpenoids (1-2), jughopanes A (1) and jughopanes B (2), along with seventeen known ones (3-19), were isolated from the fresh pericarps of Juglans hopeiensis Hu. Their structures were settled by integrated spectroscopic techniques. All isolates were tested for their cytotoxic activities and the results showed that 7 exhibited moderate cytotoxicities against MCF7 and HT29 cancer cell lines with IC50 values of 5.24 and 6.01 µM, respectively.

Pchaeglobolactone A, Spiropchaeglobosin A, and Pchaeglobosals A and B: Four Rearranged Cytochalasans from Chaetomium globosum P2-2-2.

Four novel rearranged cytochalasans (1-4) were isolated from an endophytic fungus Chaetomium globosum P2-2-2. Pchaeglobolactone A (1) possessed an unprecedented 13-aza-21-oxa-tetracyclo-[10.6.1.217,19.015,19]henicosane core. Spiropchaeglobosin A (2) was the first example of cytochalasans featuring a novel spiro[5.10]hexadecane unit. Pchaeglobosals A (3) and B (4) featured a unique 5/5/13 fused tricyclic ring system. Compounds 1-4 were tested for their antiproliferative, apoptosis, cell cycle arrest, and TRAIL-resistance-overcoming activities on cancer cell lines.

Cytochalasins from an endophytic fungus Phoma multirostrata XJ-2-1 with cell cycle arrest and TRAIL-resistance-overcoming activities.

Nine new (1-9) and four known (10-13) [13]cytochalasins, along with three known 24-oxa[14]cytochalasins (14-16), were isolated from the culture of Phoma multirostrata XJ-2-1, an endophytic fungus obtained from the fibrous root of Parasenecio albus. Their structures were elucidated by interpretation of the nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS). The absolute configurations were assigned by single-crystal X-ray crystallography, modified Mosher's method, and by analysis of their experimental electronic circular dichroism (ECD) spectra. Compound 6 could induce cell cycle arrest at G2-phase in CT26 and A549 cells, and displayed moderate cytotoxicity against CT26 and A549 cell lines with IC50 values of 6.03 and 5.04 µM, respectively. Co-treatment of 7-9, 13 and 16 with tumor necrosis factor related apoptosis inducing ligand (TRAIL) could significantly decrease the cell viability of A549, which revealed that cytochalasins could possibly be a new group of TRAIL sensitizers in lung cancer therapy.

Ergocytochalasin A, a polycyclic merocytochalasan from an endophytic fungus Phoma multirostrata XJ-2-1.

Ergocytochalasin A (1), an unprecedented merocytochalasan formed via Diels-Alder cycloaddition of a cytochalasin with an ergosterol, was isolated from an endophytic fungus Phoma multirostrata XJ-2-1. Compound 1 possessed a unique 5/6/14/6/5/6/6/6 fused octacyclic ring system and its structure was established by detailed NMR and HRESIMS spectroscopic analyses. The absolute configuration of 1 was determined by single-crystal X-ray diffraction. A plausible biogenetic pathway of 1 was postulated. Compound 1 was evaluated for its cytotoxicity against six cancer cell lines and showed inhibitory effects with IC50 values ranging from 6.92 to 26.63 µM. The in vitro immunosuppressive activity of 1 against ConA-induced T cell and LPS-induced B cell proliferation, as well as its antiviral activity against Human dengue virus type 3 (DV3), influenza A virus (H1N1) and respiratory syncytial virus (RSV), was also evaluated. Ergocytochalasin A is the first example of a merocytochalasan which consists of one cytochalasin moiety and one ergosterol moiety. Containing eighteen chiral centers, ergocytochalasin A owns a folded framework, which makes it extremely compact in space.

Resorcylic Acid Lactones from an Ilyonectria sp.

Twelve new resorcylic acid lactones (RALs) including three new 16-membered RALs (1a, 1b and 2), eight new 14-membered RALs (3-10), and one new 12-membered RAL (11), along with five known 14-membered RALs (12-16), were identified from the fermentation of the soil-derived fungus Ilyonectria sp. sb65. Their structures were established by detailed analyses of 1D and 2D NMR, HRESIMS, and X-ray diffraction crystallography. All new compounds were evaluated for their cytotoxic effects against three human cancer cell lines, along with their potential as TRAIL sensitizers in TRAIL-resistant A549 human lung adenocarcinoma cells and their in vitro immunosuppressive effects against ConA-induced T-cell and LPS-induced B-cell proliferation.

Trichothecenes from an Endophytic Fungus Alternaria sp. sb23.

Three new (alterchothecenes A - C, 1:  -3: ) and 3 known (4:  -6: ) trichothecenes, along with 9 known compounds (7:  -15: ), were isolated from the culture of Alternaria sp. sb23, an endophytic fungus separated from the root of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by spectroscopic analyses, and the absolute configurations of 1: -3: were determined through comparison of the experimental electronic circular dichroism (ECD) spectra and optical rotations with similar analogues. In vitro cytotoxicity tests of compounds 1: -6: against human HT-29 colon carcinoma and human MCF-7 breast cancer cell lines indicated that 4: -6: exhibited significant cytotoxic effects, with IC50 values ranging from 0.89 to 9.38 µM. And the potential of compounds 1: -6: as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitizers in HT-29 cells was evaluated. The results revealed that combination treatment of TRAIL with compounds 1: -6: synergistically decreased cell viability compared with the sole treatment with those compounds.

Triterpenoids from the barks of Juglans hopeiensis.

Nine undescribed triterpenoids (jughopenoids A-I), including seven nortriterpenoids and two normal triterpenoids, together with fourteen known analogues, were isolated from the barks of Juglans hopeiensis Hu. The structures of the undescribed triterpenoids were established by integrated spectroscopic analysis and single crystal X-ray diffraction. Jughopenoid A represented an unprecedented lupane-type nortriterpenoid with a five-membered lactone ring A. Selected isolates were tested for their cytotoxic effects against human HT-29 colon carcinoma, human HepG2 hepatocellular carcinoma, and human PC-3 prostate cancer cell lines. Their immunosuppressive activities against ConA-induced T cell proliferation and LPS-induced B cell proliferation were also evaluated.

Diarylheptanoids from the fresh pericarps of Juglans hopeiensis.

Ten new diarylheptanoids (1-10), including five diarylether-type (1-5), three biaryl-type (6-8), and two linear type (9-10), along with eighteen known ones, were isolated from the fresh pericarps of Juglans hopeiensis Hu. Their structures were settled by integrated spectroscopic techniques, and their absolute configurations were determined by a combination of circular dichroism analysis, optical rotations, and NOESY experiments. Screening results showed that some isolated diarylheptanoids exhibited moderate neuroprotective effects on H2O2-induced or CoCl2-induced cellular damage in human neuroblastoma SH-SY5Y cells.