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1.
J Nat Prod ; 87(4): 966-975, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38441877

ABSTRACT

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.


Subject(s)
Aspergillus , Immunosuppressive Agents , Aspergillus/chemistry , Humans , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , Molecular Structure , Crystallography, X-Ray , Interleukin-6/metabolism , Anthraquinones/pharmacology , Anthraquinones/chemistry , Animals , Drug Screening Assays, Antitumor , T-Lymphocytes/drug effects , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Proliferation/drug effects
2.
Org Biomol Chem ; 22(11): 2271-2278, 2024 03 13.
Article in English | MEDLINE | ID: mdl-38391281

ABSTRACT

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.


Subject(s)
Ascomycota , Lignans , Humans , Lignans/chemistry , Cell Line , Indole Alkaloids , Immunosuppressive Agents , Molecular Structure
3.
Phytochemistry ; 218: 113939, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38052264

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Ascomycota , Indole Alkaloids , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , HeLa Cells , Apoptosis , Molecular Structure
4.
J Nat Prod ; 87(1): 141-151, 2024 01 26.
Article in English | MEDLINE | ID: mdl-38128907

ABSTRACT

Twelve new austalide meroterpenoids (1-12) were isolated from the endophytic fungus Diaporthe sp. XC1211. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of compounds 1, 3, 4, and 6 were established by single-crystal X-ray diffraction, whereas those for the others were established by experimental electronic circular dichroism (ECD) data analysis. Compounds 1-12 represent a rare class of austalides with a 24α-CH3. Compounds 2 and 5 demonstrated potent proliferation inhibitory effects against LPS-induced B cells with IC50 values of 6.7 (SI = 3.6) and 3.8 (SI > 13) µM, respectively. Compounds 2 and 5 decreased the secretion of IL-6 in LPS-induced B cells in a dose-dependent manner.


Subject(s)
Fungi , Lipopolysaccharides , Molecular Structure , Lipopolysaccharides/pharmacology , Crystallography, X-Ray , Circular Dichroism
5.
Fitoterapia ; 171: 105691, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37757922

ABSTRACT

Four undescribed neolignan glycosides, bletineosides A-D (1-4) were isolated from the pseudobulbs of Bletilla striata. Their structures with absolute configurations were elucidated on the basis of spectroscopic analyses, along with acidic hydrolysis reactions and ECD experiments. All isolates were evaluated for their neuroprotective activities against glutamate-induced PC12 cell injury. Compound 3 and 4 showed significantly neuroprotective effects at the concentration of 10 µM when compared with the model group. Compounds 1-4 represented the first examples of neolignan glycosides from the genus Bletilla. This study disclosed the potency of Bletilla striata as a new source of anti-neurodegenerative agents.


Subject(s)
Lignans , Orchidaceae , Molecular Structure , Glutamates , Glycosides/pharmacology , Lignans/pharmacology
6.
Phytochemistry ; 214: 113821, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37567352

ABSTRACT

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).


Subject(s)
Antineoplastic Agents , Asteraceae , Sesquiterpenes , Polycyclic Sesquiterpenes , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Lactones/pharmacology , Lactones/chemistry , Asteraceae/chemistry , Isomerism , Molecular Structure
7.
Bioorg Chem ; 139: 106745, 2023 10.
Article in English | MEDLINE | ID: mdl-37499531

ABSTRACT

Eight unreported andrastin-type meroterpenoids, namely peniandrastins A-H (1-8), along with six known analogues (9-14), were isolated from the fermentation of a soil-derived fungus Penicillium sp.sb62. Their structures with absolute configurations were elucidated by detailed analyses of the spectroscopic data and single-crystal X-ray diffraction. Compounds 1-4 belong to a rare class of 21-nor-andrastin meroterpenoids, of which 1 bears a 10-hydroperoxyl group, and 2 and 3 feature a 6/6/6/5/5 and a 6/6/6/5/6 pentacyclic systems, respectively. Compounds 5-8 are C25 andrastin-type meroterpenoids, wherein 5 features an unprecedented cyclopentan-1-keton-3-hemiacetal moiety. Additionally, the absolute configuration of compound 9 was corroborated by single-crystal X-ray crystallography for the first time. All isolates were evaluated for their immunosuppressive activities. As a result, compounds 1, 3, 4, 7-9 and 12-14 inhibited concanavalin A-induced T cell proliferation with IC50 values ranging from 7.49 to 36.52 µM, and 1-4, 6-9 and 12-14 inhibited lipopolysaccharide-induced B cell proliferation with IC50 values ranging from 6.73 to 26.27 µM. The preliminary structure-activity relationships (SARs) of those isolates were also discussed.


Subject(s)
Penicillium , Penicillium/chemistry , Molecular Structure , Spectrum Analysis , Fungi , Structure-Activity Relationship
8.
J Nat Prod ; 86(1): 66-75, 2023 01 27.
Article in English | MEDLINE | ID: mdl-36596229

ABSTRACT

Peniandranoids A-E (1-5), five new meroterpenoids, together with three known analogues (6-8), were isolated from the fermentation of a soil-derived fungus, Penicillium sp.sb62. Their structures including absolute configurations were determined by extensive spectroscopic analysis, and the absolute configurations of compounds 1 and 5 were further elucidated by single-crystal X-ray diffraction. Peniandranoids A-E belong to a rare class of andrastin-type meroterpenoids incorporating an extra polyketide unit (a C10 polyketide unit for 1 and 2, a C9 polyketide unit for 3 and 4, and a furancarboxylic acid unit for 5). Compounds 1 and 6 exhibited favorable inhibitory activities against influenza virus A (H1N1) with EC50 values of 19 and 14 µg/mL, respectively. Compounds 3-8 exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with EC50 values ranging from 4.3 to 27 µM and lipopolysaccharide-induced B cell proliferation with EC50 values ranging from 7.5 to 23 µM, respectively.


Subject(s)
Influenza A Virus, H1N1 Subtype , Penicillium , Polyketides , Molecular Structure , Penicillium/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/chemistry
10.
Curr Med Sci ; 42(5): 905-912, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36255662

ABSTRACT

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.


Subject(s)
Antifungal Agents , Poisons , Animals , Antifungal Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Pharmaceutical Preparations
11.
Bioorg Chem ; 127: 106011, 2022 10.
Article in English | MEDLINE | ID: mdl-35841670

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Ascomycota , Antineoplastic Agents/chemistry , Apoptosis , Cell Line, Tumor , G2 Phase Cell Cycle Checkpoints , Humans , Indole Alkaloids
13.
Phytochemistry ; 201: 113287, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35724742

ABSTRACT

Twelve undescribed glucosyloxybenzyl 2-isobutylmalates, bletistrosides A-L were obtained from the pseudobulbs of Bletilla striata under the guidance of HPLC-PDA. Their structures and absolute configurations were determined by the spectroscopic analyses, along with acidic hydrolysis and alkaline hydrolysis experiments. The neuroprotective effects and the antimicrobial activities of selective compounds were evaluated. Bletistroside G exhibited potential neuroprotective effect against glutamate-induced PC12 cell injury, with improving cell viabilities by 11.24% compared to the model group at 10 µM. Bletistrosides A, B, G, and L showed weak antimicrobial activities against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, however, bletistroside G showed obviously selective inhibition against P. aeruginosa.


Subject(s)
Anti-Infective Agents , Orchidaceae , Anti-Infective Agents/pharmacology , Chromatography, High Pressure Liquid , Orchidaceae/chemistry , Staphylococcus aureus
14.
Bioorg Chem ; 123: 105796, 2022 06.
Article in English | MEDLINE | ID: mdl-35421731

ABSTRACT

Eleven previously undescribed radicicol-type resorcylic acid lactones (RALs), namely ilyomycins A - K (1-9, 10a and 10b), were isolated and identified from the fermented rice culture of a soil-derived fungus, Ilyonectria sp. (strain sb65). Their gross structures were determined by extensive spectroscopic data, and the absolute configurations were elucidated by single-crystal X-ray diffraction, the modified Mosher's method, and Rh2(OCOCF3)4-induced electronic circular dichroism (ICD) experiment. Among them, 10a and 10b were a pair of inseparable regioisomers via intramolecular transacetylation. Compounds 3, 7, 8 and 10a/10b displayed immunosuppressive activities against T cell proliferation with IC50 values ranging from 1.2 to 21.7 µM, and against B cell proliferation with IC50 values ranging from 1.1 to 20.1 µM, which suggested that the α, ß-unsaturated ketone from C-8 to C-10 was an important pharmacophore. Further study revealed that ilyomycin C (3) exerted anti-proliferative effect on T lymphocytes through Hsp90 inhibition.


Subject(s)
Hypocreales , Lactones , Immunosuppressive Agents/pharmacology , Lactones/chemistry , Lactones/pharmacology , Macrolides , Molecular Structure , Soil
15.
Planta Med ; 88(14): 1299-1310, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35100652

ABSTRACT

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.


Subject(s)
Ascomycota , Cytochalasins , Humans , Cytochalasins/pharmacology , Cytochalasins/chemistry , Molecular Structure , A549 Cells
16.
Org Biomol Chem ; 20(3): 694-700, 2022 01 19.
Article in English | MEDLINE | ID: mdl-34989382

ABSTRACT

Three pairs of new heterodimeric polyketide enantiomers, (±)-usphenethylones A-C (1-3), were isolated from the culture extract of Aspergillus ustus 3.3904. Compounds 1-3 present two heterodimerization patterns by a phenylethyl unit connected to an α-pyrone moiety, of which usphenethylones A-B (1-2) feature a 2,6,18-trioxa-tetracyclo-[8.8.0.03,8.011,16]octadecane core and usphenethylone C (3) possesses a 2-phenyl-3,4-dihydro-pyrano[4,3-b]pyran-5-one scaffold. The structures of (±)-1-3 were elucidated based on spectroscopic data analyses, and their absolute configurations were determined by single-crystal X-ray diffraction analysis and ECD calculation. Plausible biosynthetic pathways for 1-3 were proposed. Compounds (+)-3 and (-)-3 exhibited moderate inhibitory effects against ConA-induced T cell and LPS-induced B cell proliferation.


Subject(s)
Aspergillus , Polyketides , Aspergillus/chemistry , Crystallography, X-Ray , Models, Molecular , Molecular Conformation , Polyketides/chemistry , Stereoisomerism
17.
Planta Med ; 88(14): 1293-1298, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34963184

ABSTRACT

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.


Subject(s)
Alkaloids , Chaetomium , Chaetomium/chemistry , Chaetomium/metabolism , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Cytochalasins/pharmacology , Cytochalasins/chemistry , Molecular Structure
18.
Fitoterapia ; 156: 105093, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34856341

ABSTRACT

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.


Subject(s)
Anti-Infective Agents/pharmacology , Asteraceae/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Candida albicans/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Escherichia coli/drug effects , Hep G2 Cells , Humans , MCF-7 Cells , Magnetic Resonance Spectroscopy , Melanoma, Experimental , Mice , Plant Extracts/pharmacology , Sesquiterpenes/pharmacology , Staphylococcus aureus/drug effects , X-Ray Diffraction
19.
Bioorg Chem ; 118: 105482, 2022 01.
Article in English | MEDLINE | ID: mdl-34801946

ABSTRACT

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.


Subject(s)
Apoptosis/drug effects , Immunosuppressive Agents/pharmacology , Lactones/pharmacology , Podospora/chemistry , T-Lymphocytes/drug effects , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/metabolism , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , Lactones/chemistry , Lactones/isolation & purification , MAP Kinase Signaling System , Male , Mice , Mice, Inbred BALB C , Molecular Structure , Proto-Oncogene Proteins c-akt , Structure-Activity Relationship , T-Lymphocytes/metabolism
20.
Org Lett ; 23(24): 9620-9624, 2021 12 17.
Article in English | MEDLINE | ID: mdl-34881899

ABSTRACT

Aspersteroid A (1), a highly rearranged 1(10 → 6)-abeo-18,22-cyclosterol, together with two new 18,22-cyclosterols (2 and 3), was isolated from the culture extract of Aspergillus ustus NRRL 275. Their structures were determined by spectroscopic analysis, X-ray diffraction, modified Mosher's method, and Rh2(OCOCF3)4-induced electronic circular dichroism experiments. Compound 1 represents a new carbon skeleton with an uncommon 6/6/6/5/5 ring system, which is presumably biosynthesized from A-ring scission, double 1,2-shifts, and C-18/C-22 cyclization. Compound 1 exhibited potent immunosuppressive and antimicrobial activities.


Subject(s)
Aspergillus
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