Pulchelloid A, a sesquiterpene lactone from the Canadian prairie plant Gaillardia aristata inhibits mitosis in human cells.

BACKGROUND: The Canadian prairie ecosystem presents a rich source of natural products from plants that are subjected to herbivory by grazing mammals. This type of ecological competition may contribute to the production of natural products of interest in cell biology and medical research. We provide the first biological description of the sesquiterpene lactone, pulchelloid A, which we isolated from the prairie plant, Gaillardia aristata (Asteraceae) and report that it inhibits mitosis in human cells. METHODS AND RESULTS: We found that G. aristata (Blanket flower) extracts were cytotoxic to human cell lines and used phenotypic assays to characterize the bioactivity of extracts. Before dying, cells were characterized by a rounded morphology, phospho-histone H3 signals, mitotic spindles, and active Cdk1. By biology-guided fractionation of Gaillardia extracts, we isolated a sesquiterpene lactone named pulchelloid A. We used immunofluorescence microscopy and observed that cells treated with pulchelloid A have phospho-histone H3 positive chromosomes and a mitotic spindle, confirming that they were in mitosis. Treated cells arrest with an unusual phenotype; they enter a prolonged mitotic arrest in which the spindles become multipolar and the chromosomes acquire histone γH2AX foci, a hallmark of damaged DNA. CONCLUSIONS: We propose that pulchelloid A, a natural product present in the prairie plant Gaillardia aristata, delays cells in mitosis. There is a growing body of evidence that a small number of members of the sesquiterpene lactone chemical family may target proteins that regulate mitosis.

Structures of Nahuoic Acids B-E Produced in Culture by a Streptomyces sp. Isolated from a Marine Sediment and Evidence for the Inhibition of the Histone Methyl Transferase SETD8 in Human Cancer Cells by Nahuoic Acid A.

Nahuoic acids A-E (1-5) have been isolated from laboratory cultures of a Streptomyces sp. obtained from a tropical marine sediment. The structures of the new polyketides 2-5 were elucidated by analysis of spectroscopic data of the natural products and the chemical derivatives 6 and 7. Nahuoic acids 1-5 are in vitro inhibitors of the histone methyltransferase SETD8, and nahuoic acid A (1) and its pentaacetate derivative 8 inhibit the proliferation of several cancer cells lines in vitro with modest potency. At the IC50 for cancer cell proliferation, nahuoic acid A (1) showed selective inhibition of SETD8 in U2OS osteosarcoma cells that reflect its selectivity against a panel of pure histone methyl transferases. A cell cycle analysis revealed that the cellular toxicity of nahuoic acid A (1) is likely linked to its ability to inhibit SETD8 activity.

Potential of Arabica Coffee Beans from Northern Thailand: Exploring Antidiabetic Metabolites through Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) Metabolomic Profiling across Diverse Postharvest Processing Techniques.

Coffee, a widely consumed beverage worldwide, undergoes postharvest methods that influence its physicochemical characteristics, while roasting modulates its composition, affecting sensory attributes. This study investigates the impact of distinct postharvest methods (washed and natural) on the antidiabetic activities, including α-amylase and DPP4, as well as the phytochemical profiling of geological indicator (GI) coffee beans (Coffea arabica L.). The results indicate notable differences in antidiabetic activity and phytochemical profiles between washed and natural processing methods. Coffee beans processed naturally exhibit significant suppression of DPP4 and α-amylase activities (p-value < 0.01) compared to beans processed using the washed technique. TLC profiling using the ratios of the solvent systems of ethyl acetate/dichloromethane (DCM) and acetone/DCM as separation solvents reveals dominant spots for the washed technique. LC-MS/MS-based untargeted metabolomics analysis using principle component analysis (PCA) clearly segregates samples processed by the natural and washed techniques without any overlap region. A total of 1114 phytochemicals, including amino acids and short peptides, are annotated. The natural processing of coffee beans has been shown to yield a slightly higher content of chlorogenic acid (CGA) compared to the washed processing method. Our findings highlight the distinct bioactivities and phytochemical compositions of GI coffee beans processed using different techniques. This information can guide consumers in choosing coffee processing methods that offer potential benefits in terms of alternative treatment for diabetes.

Rearranged benzophenones and prenylated xanthones from Garcinia propinqua twigs.

The first phytochemical investigation of Garcinia propinqua has led to the isolation and identification of three new compounds, including two rearranged benzophenones, doitunggarcinones A (1) and B (2), and a xanthone, doitunggarcinone C (3), together with seven known compounds (4-10). The structures of 1-3 were elucidated on the basis of spectroscopic methods, including UV, IR, NMR, and MS. The antibacterial activity of the 10 isolates was evaluated against Escherichia coli TISTR 780, Salmonella typhimurium TISTR 292, Staphylococcus aureus TISTR 1466, and methicillin-resistant Staphylococcus aureus (MRSA) SK1.

Absolute configuration of xerophenone A.

The title compound, C(33)H(42)O(5), known as xerophenone A {systematic name: (1R,3R,4R,6S,8E,10R)-10-hy-droxy-8-[hy-droxy(phen-yl)methyl-ene]-4-methyl-1,6-bis-(3-methyl-but-2-en-1-yl)-3-(3-methyl-but-3-en-1-yl)-11-oxatricyclo-[4.3.1.1(4,10)]undecane-7,9-dione} is a naturally occurring rearranged benzophenone compound which was isolated from the twigs of Garcinia propinqua. The absolute configuration was determined by refining the Flack parameter to 0.18 (16). The absolute configurations at positions 1, 3, 4, 6 and 10 of the xerophenone A are R, R, R, S and R. In the mol-ecule, the cyclo-hexane-1,3-dione, tetra-hydro-2H-pyran and tetra-hydro-furan rings adopt twisted boat, standard chair and envelope conformations, respectively. The 3-methyl-but-3-en-1-yl substituent is disordered over two sets of sites in a 0.771 (11):0.229 (11) ratio. An intra-molecular O-H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, mol-ecules are linked by O-H⋯O and weak C-H⋯O inter-actions into a chain along the a axis. A very weak C-H⋯π inter-action and C⋯O short contact [2.989 (2) Å] are also present.

Derrisrobustones A-D, isoflavones from the twig extract of Derris robusta (DC.) Benth. and their α-glucosidase inhibitory activity.

Three previously undescribed isoflavones, derrisrobustones A-C, and a previously undescribed natural isoflavone, derrisrobustone D, along with eight known isoflavones, were isolated from the twig extract of Derris robusta (DC.) Benth. All structures were identified by extensive spectroscopic analysis. Derrisrobustones A-C were obtained as scalemic mixtures and were resolved by chiral HPLC. The (1″R, 2″R) absolute configuration of (+)-derrisrobustone B was established by single-crystal X-ray crystallography using Cu Kα radiation. The absolute configurations of derrisrobustones A and C were determined by analysis of experimental and calculated ECD data. All compounds were evaluated for their α-glucosidase inhibitory activity. Of these, derrubone displayed the best α-glucosidase inhibitory activity with an IC50 value of 64.2 µM.

Inhibition of nitric oxide production by clerodane diterpenoids from leaves and stems of Croton poomae Esser.

Chromatographic separation of crude extracts from the leaves and stems of Croton poomae Esser led to the isolation of two new clerodane diterpenes crotonolide K (1) and furocrotinsulolide A acetate (2) and six known clerodane diterpenes (3-8), together with twelve known compounds (9-20). Their structures were established from spectroscopic analysis. The clerodane diterpenoids 1-8 were evaluated for inhibition of nitric oxide (NO) production in LPS-activated RAW 264.7 macrophages. Compounds 1, 2, 5, 7 and 8 showed potent inhibitory effects, with IC50 values ranging from 32.19 to 48.85 µM, which is better than both the standard drugs indomethacin (154.5 µM) and dexamethasone (56.28 µM).

Bioactive secondary metabolites from roots of Cissus rheifolia planch.

Two new aromadendrin rhamnosides, cissusfoliate A (1) and 3-epi-cissusfoliate A (2) together with seven known compounds (3-9) were isolated from the roots of Cissus rheifolia Planch. Their structures were determined by extensive spectroscopic methods. The absolute configurations of compounds 1-5 were assigned by combination of the J coupling constant values of H-2 and H-3 and the comparison of their experimental ECD spectra with those reported in literature. Compounds 1, 3 and 5-8 showed antioxidant effects on ORAC, ATBS and DPPH assays as well as antibacterial activity against six pathogenic bacterial strains. Their cytotoxicity against Hela, KB, MCF-7, HepG2 and HT-29 cell lines were also evaluated.

Bioactive xanthoquinodins and epipolythiodioxopiperazines from Chaetomium globosum 7s-1, an endophytic fungus isolated from Rhapis cochinchinensis (Lour.) Mart.

A new xanthoquinodin B9 (1), together with two known xanthoquinodins, xanthoquinodin A1 (2) and xanthoquinodin A3 (3), three epipolythiodioxopiperazines, chetomin (4), chaetocochin C (5) and dethio-tetra(methylthio)chetomin (6), and four other compounds, chrysophanol (7), emodin (8), alatinone (9), and ergosterol (10) were isolated from the endophytic fungus Chaetomium globosum 7s-1, isolated from Rhapis cochinchinensis (Lour.) Mart. All isolated structures were established based on their spectroscopic data analyses. Compounds 1-6 showed antibacterial activity against Gram positive bacteria with MICs ranging from 0.02 pM to 10.81 µM. Compounds 1-6 also exhibited cytotoxicity against KB, MCF-7 and NCI-H187 cancer cell lines (IC50 0.04-18.40 µM). However, they were cytotoxic towards a normal cell line (Vero cell) with IC50 values ranging from 0.04 to 3.86 µM.

Spirosteroids and α-glucosidase inhibitory norlignans from Asparagus racemosus Willd. roots.

Three undescribed spirosteroids, asparacemosones A-C, an undescribed spiro-21-norsteroid, asparacemosone D, along with seven known compounds were isolated from Thai herbal plant Asparagus racemosus Willd. roots. Their structures were elucidated by spectroscopic analysis including NMR, UV, IR and mass spectrometry. The absolute configurations of asparacemosones A, B, and D were determined by single crystal X-ray diffraction using CuKα radiation. Among the isolated compounds, the norlignan nyasol and three acetylenic norlignans demonstrated potent α-glucosidase inhibition, with IC50 values ranging from 0.003 to 0.004 µM which is 5 × 104 fold more potent than the standard acarbose.

Resolution and identification of scalemic caged xanthones from the leaf extract of Garcinia propinqua having potent cytotoxicities against colon cancer cells.

A new scalemic 8,8a-dihydro caged xanthone (1) was isolated from the leaf extract of Garcinia propinqua. Five other known natural products, the three caged xanthones (2, 5 and 6) and the two neocaged xanthones, (3 and 4) were also isolated as scalemic mixtures. Their structures were characterized by spectroscopic methods. The enantiomeric ratios (er) of compounds 1-6 ranged from 1:0.7 to 1:0.9. These compounds were also resolved by semipreparative chiral HPLC. The absolute configurations of (+)-2 and (+)-3 were determined by single-crystal X-ray diffraction analysis using Cu Kα radiation while the absolute configurations of the other compounds were determined by comparisons of their ECD spectra. Compounds (-)-4, (+)-4, (-)-5, (+)-5, and (-)-6 showed potent cytotoxicities against a colon cancer cell line HCT116 with IC50 values of 2.60, 7.02, 1.47, 3.37, and 4.14µM, respectively, which were better than the standard control doxorubicin (IC50 9.74µM).

A new xanthone from the fungus Apiospora montagnei.

A new xanthone derivative, methyl 8-hydroxy-3-hydroxymethylxanthone-1-carboxylate (1), and seven known compounds, 8-hydroxy-3-methylxanthone-1-carboxylate (2), methyl 8-hydroxy-6-methylxanthone-1-carboxylate (3), ergosterol (4), cyathisterone (5), ergosta-4,6,8(14),22-tetraen-3-one (6), calvasterone (7) and 2-hexyl-3-methylmaleic anhydride (8) were first isolated from the fungus Apiospora montagnei. Their structures were elucidated on the basis of spectroscopic analysis (UV, IR, MS, 1D, and 2D NMR). Compounds 5 and 6 showed weak to very weak cytotoxicity against cancer cell lines, NCI-H187 and KB.

New Benzophenones and Xanthones from Cratoxylum sumatranum ssp. neriifolium and Their Antibacterial and Antioxidant Activities.

Two new benzophenones (1 and 2) and four new xanthones (4-6 and 17) together with 24 known compounds (3, 7-16, and 18-30) were isolated from the roots and twigs of Cratoxylum sumatranum ssp. neriifolium. Their structures were elucidated by spectroscopic methods. Compounds 5 and 26 showed antibacterial activity against Micrococcus luteus, Bacillus cereus, and Staphylococcus epidermis with minimum inhibitory concentrations ranging from 4 to 8 µg/mL, whereas compounds 7, 20, and 26 displayed selective antibacterial activities against Staphylococcus aureus (8 µg/mL), Salmonella typhimurium (4 µg/mL), and Pseudomonas aeruginosa (4 µg/mL), respectively. The radical scavenging effects of some isolated compounds were investigated. Compounds 11 and 21 exhibited potent activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) with IC50 values of 7.0 ± 1.0 and 6.0 ± 0.2 µM, respectively.

Dammarane terpenoids from the fruits of Dysoxylum mollissimum.

Two new dammaranes, dysomollisol (1) and dysomollisone (2), along with seven known compounds (3-9) were isolated and identified from the fruits of Dysoxylum mollissimum. The structures of these compounds were determined on the basis of spectroscopic analyses, including 1D and 2D NMR, UV, IR and mass spectrometry. The antibacterial activity and cytotoxicity against epidermoid carcinoma of oral cavity (KB) cell line of compounds 1-9 were evaluated.

Antibacterial compounds from Glycosmis puberula twigs.

The first phytochemical investigation of Glycosmis puberula twigs led to the isolation and identification of a new quinolone alkaloid, glycosmispuberulone (1), along with ten known compounds (2-11). The structures were elucidated by spectroscopic analyses and comparison with previously reported data. Their antibacterial activities against Gram-positive and Gram-negative bacteria were also evaluated.

Antibacterial compounds from Zanthoxylum rhetsa.

A new amide, zanthorhetsamide (1), along with nine known compounds (2-10) was isolated from the roots and stem barks of Zanthoxylum rhetsa. The structure was characterized by spectroscopic methods. In addition, the antibacterial activity of the isolates was evaluated. Dihydrochelerythrine (4) exhibited strong activity against methicillin-resistant Staphylococcus aureus SK1 and moderate activity against Escherichia coli TISTR 780 with MIC values of 8 and 16 µg/mL, respectively.