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.

Bioassay-guided isolation and identification of antidiabetic compounds from Garcinia cowa leaf extract.

Garcinia cowa Roxb. ex Choisy (Clusiaceae) is a Thai local edible plant, which has been used for the treatment of diabetes. The aim of this study is to discover and identify bioactive compounds related to antidiabetic properties from the leaf extract of G. cowa. α-Glucosidase inhibitory bioassay-guided isolation of the ethyl acetate extract of the leaves of G.cowa resulted in the isolation and identification of 11 compounds. Of these, a decahydro-1H-xanthene derivative, garciniacowone K (1), was identified as a novel compound. Their structures were characterized by spectroscopic data and by comparison of their NMR spectroscopic data with those previously reported. All compounds were evaluated for their α-glucosidase inhibitory and glucose consumption activities. Compound 2 showed the highest efficacy in inhibiting α-glucosidase enzyme and promoting glucose consumption activity by 3T3-L1 cells, with IC50 values of 0.5 µM and 13.1 µM, respectively, without causing toxicity to cells.

In Vitro Anti-Inflammatory, Anti-Oxidant, and Cytotoxic Activities of Four Curcuma Species and the Isolation of Compounds from Curcuma aromatica Rhizome.

The genus Curcuma is part of the Zingiberaceae family, and many Curcuma species have been used as traditional medicine and cosmetics in Thailand. To find new cosmeceutical ingredients, the in vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four Curcuma species as well as the isolation of compounds from the most active crude extract (C. aromatica) were investigated. The crude extract of C. aromatica showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with an IC50 value of 102.3 µg/mL. The cytotoxicity effect of C. aeruginosa, C. comosa, C. aromatica, and C. longa extracts assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay at 200 µg/mL were 12.1 2.9, 14.4 4.1, 28.6 4.1, and 46.9 8.6, respectively. C. aeruginosa and C. comosa presented apoptosis cells (57.7 3.1% and 32.6 2.2%, respectively) using the CytoTox-ONE™ assay. Different crude extracts or phytochemicals purified from C. aromatica were evaluated for their anti-inflammatory properties. The crude extract of C. aromatica showed the highest potential to inhibit NF-κB activity, followed by C. aeruginosa, C. comosa, and C. longa, respectively. Among the various purified phytochemicals curcumin, germacrone, curdione, zederone, and curcumenol significantly inhibited NF-κB activation in tumor necrosis factor (TNF) stimulated HaCaT keratinocytes. Of all compounds, curcumin was the most potent anti-inflammatory.

α-Glucosidase inhibitory and nitric oxide production inhibitory activities of alkaloids isolated from a twig extract of Polyalthia cinnamomea.

The first phytochemical investigation of Polyalthia cinnamomea led to the isolation and identification of two new oxoprotoberberine alkaloids, (-)-(13aS)-polyalthiacinnamines A and B, together with eleven known compounds. The structures of the new compounds were elucidated by extensive spectroscopic methods. The absolute configuration of miliusacunine E and consanguine B was established by X-ray diffraction analysis using Cu Kα radiation and ECD spectra, whereas the absolute configurations of polyalthiacinnamines A and B were established by comparison of their ECD spectra and specific rotations with those of miliusacunine E and consanguine B. Compounds 1-4, 6, and 8 exhibited α-glucosidase inhibitory activities (IC50 values ranging from 11.3 to 57.9 µM) better than a positive control (acarbose, IC50 83.5 µM). Compound 2 also exhibited NO production inhibitory activity with an IC50 value of 24.4 µM (indomethacin, a positive control, IC50 = 32.2 µM).

Chemical Composition of Essential Oils from Different Parts of Zingiberkerrii Craib and Their Antibacterial, Antioxidant, and Tyrosinase Inhibitory Activities.

The essential oils of the fresh rhizomes; flowers; and leaves of Zingiber kerrii Craib were investigated using different extraction techniques; including solid-phase microextraction (SPME), hydrodistillation (HD), and organic solvent (OS), and characterized by gas chromatography-mass spectrometry (GC-MS). A total of 37 SPME; 19 HD; and 36 OS compounds were identified from the rhizome extract of Z. kerrii; with the major components being α-pinene; ß-pinene; and terpinen-4-ol; respectively. From the flower extract; 16 SPME; 2 HD; and 10 OS compounds were identified; (E)-caryophyllene was found as a major compound by these techniques. The leaf extract exhibited 20 SPME; 13 HD; and 14 OS compounds; with α-pinene; (E)-caryophyllene; and n-hexadecanoic acid being the major compounds; respectively. The rhizome extract showed tyrosinase inhibitory activity of 71.60% and a total phenolic content of 22.4 mg gallic acid/g. The IC50 values of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays were 25.2 µg/mL and 153.6 µg/mL; respectively; and the ferric ion reducing antioxidant power (FRAP) assay value was 318.5 µM ascorbic acid equivalent (AAE)/g extract. The rhizome extract showed weak antibacterial activity. This extract showed no adverse toxicity in human keratinocyte (HaCaT) cell lines at concentrations below 200 µg/mL.

Antibacterial and cytotoxic activities of phenolic constituents from the stem extracts of Spatholobus parviflorus.

A new 2-arylbenzofuran, spathobenzofuran (1), together with ten known compounds including a 2-arylbenzofuran, three pterocarpans and six isoflavones were isolated from the acetone crude extract of the stems of Spatholobus parviflorus. All compounds were characterised by spectroscopic methods. Compound 4 was active (MIC 8 µg/mL) against Gram-negative Pseudomonas aeruginosa TISTR 781 while compound 2 had modest activity against Gram-positive Staphylococcus aureus TISTR 1466 with a MIC value of 16 µg/mL. All isolated compounds showed no cytotoxicity against Vero and KB cells.

Phloroglucinol Benzophenones and Xanthones from the Leaves of Garcinia cowa and Their Nitric Oxide Production and α-Glucosidase Inhibitory Activities.

Five new compounds-two phloroglucinol benzophenones, garciniacowones F (1) and G (2), and three xanthones, garciniacowones H (3), I (4), and J (5)-together with seven known xanthones (6-12) were isolated from the fresh leaves of Garcinia cowa. Their structures were elucidated by detailed analysis of NMR and MS data. Compounds 1 and 2 are phloroglucinol benzophenones containing a polyprenylated bicyclo[3.3.1]nonane ring system, while compounds 3-5 are rare xanthones having farnesyl (3 and 5) and geranylgeranyl (5) units at C-8. Compounds 1, 3, 4, 7, 8, and 10 exhibited inhibitory effects on NO production in LPS-induced RAW264.7 macrophage cells with IC50 values ranging from 5.4 to 18.6 µM. Compounds 4 and 8 had α-glucosidase inhibitory activities with IC50 values of 15.4 and 11.4 µM, respectively, which were more potent than that of the acarbose control.

Dasymaschalolactams A-E, Aristolactams from a Twig Extract of Dasymaschalon dasymaschalum.

Five new aristolactam alkaloids (1-5), dasymaschalolactams A-E, and the first isolation of dasymaschalolactone (17) as a natural product, together with 19 known compounds (6-16 and 18-25) were isolated from the twig extract of Dasymaschalon dasymaschalum. Their structures were elucidated by spectroscopic methods as well as comparisons made from the literature. Compounds 20 and 21 showed α-glucosidase inhibitory activities with IC50 values of 4.5 and 24.7 µM, respectively.

Uvarialuridols A-C, three new polyoxygenated cyclohexenes from the twig and leaf extracts of Uvaria lurida.

The first phytochemical investigation of Uvaria lurida resulted in the isolation and identification of three new polyoxygenated cyclohexenes, (+)-(1R,2S,3R,6S)-uvarialuridols A-C (1-3), together with 10 known compounds (4-13). All new structures were elucidated by spectroscopic methods and HRESIMS. The absolute configurations of compounds 1 and 5 were confirmed by X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of compounds 2-4 were identified from comparisons of their specific rotations and ECD spectra with those of known compounds. Compound 11 showed α-glucosidase inhibitory activity with an IC50 value of 30 µM which was better than the standard control, acarbose (74 µM) whereas, compound 10 exhibited nitric oxide (NO) production inhibitory activity with an IC50 value of 37 µM.

Antibacterial and Inhibitory Activities against Nitric Oxide Production of Coumaronochromones and Prenylated Isoflavones from Millettia extensa.

A chemical investigation of leaf and root extracts of Millettia extensa led to the isolation and structural elucidation of four new prenylated isoflavones, millexatins G-J (1-4), and three new coumaronochromones, millexatins K-M (5-7), along with 16 known compounds. The structures of the new compounds were determined on the basis of NMR and MS data. Compound 4 is a rare isoflavone having a 2-hydroxyethyl moiety at C-8, whereas the structures of compounds 5-7 formally arise from a ring closure through HO-2' and C-2. The absolute configurations at the C-2 and C-3 positions of 5 and 6 were determined from their ECD spectra through comparison with those of previously reported compounds. Most of compounds were evaluated for their inhibitory effects against nitric oxide (NO) production on RAW264.7 macrophages and their antibacterial activities. Compounds 18 and 19 inhibited NO production with IC50 values of 8.5 and 14.3 µM, respectively. Compounds 13 and 14 showed antibacterial activity against various Gram-positive bacteria with MIC values ranging from 2 to 8 µg/mL.

Mallopenins A-E, Antibacterial Phenolic Derivatives from the Fruits of Mallotus philippensis.

The chromatographic separation of the components of the acetone extract of Mallotus philippensis fruits yielded five new phenolic compounds including two chalcones, 1 and 3, a functionalized phloroglucinol, 2, two flavanones, 4 and 5, and six known compounds. The structures of 1-5 were confirmed by NMR and mass analyses. Racemic compounds 1 and 2 were separated by chiral-phase HPLC, and the absolute configuration of (+)-1 was confirmed by X-ray diffraction studies and ECD spectroscopic data. The configurations of the enantiomers of 2 were defined by comparison of its ECD data with those of (+)-1. Compounds 6 and 7 exhibited significant antibacterial activities, with MIC values ranging from 3.8 to 15.5 µM.

A tocotrienol quinone dimer and xanthones from the leaf extract of Garcinia nigrolineata.

Four new compounds (1-4) together with six known compounds (5-10) were isolated from the leaf extract of Garcinia nigrolineata. Compound 4 is a rare tocotrienol quinone dimer. The structures were elucidated based on NMR and MS data. All isolated compounds were evaluated for their antibacterial activities.

Coumarins and flavones from the fruit and root extracts of Micromelum integerrimum.

A phytochemical investigation of the fruit and root extracts of Micromelum integerrimum resulted in the isolation and identification of a new compound, integerravone (1), together with 23 known compounds (2-24). Their structures were characterized by spectroscopic methods as well as comparisons made from the literature. Compounds 2, 3-15, 17-18 and 20-23 were evaluated for their cytotoxicities against the colon cancer cell line, HCT116. All of them were inactive at 50 µM. Most of the phenolic compounds were evaluated for their antioxidant activity using the DPPH assay. Compounds 14 and 22-24 showed antioxidant activity with IC50 values ranging from 24.83-135.05 µM.

Antioxidant neolignans from the twigs and leaves of Mitrephora wangii HU.

Two new compounds, odoratisol E (1) and decurrenal A (2), together with 12 known compounds were isolated from the twig and leaf extracts of Mitrephora wangii HU (Annonaceae). All structures were elucidated by spectroscopic methods. The structure of compound (+)-6 was also confirmed by X-ray diffraction analysis. The absolute configurations of odoratisol E and decurrenal A were determined by comparison of their electronic circular dichroism (ECD) spectra with those of related known compounds. Most of the isolated compounds were evaluated for their antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Compounds 4 and (+)-6 displayed potent ABTS radical scavenging activity with IC50 values of 11.9 ±â€¯1.8 and 10.8 ±â€¯1.7 µM, respectively, which is better than that of standard compound, ascorbic acid, (IC50 = 19.3 ±â€¯0.1 µM). Compound 9 showed moderate DPPH radical scavenging activity with an IC50 value of 38.7 ±â€¯0.8 µM.

Antibacterial Prenylated Isoflavonoids from the Stems of Millettia extensa.

The first phytochemical investigation of the stem extract of Millettia extensa resulted in the isolation and identification of six new isoflavones, millexatins A-F (1-6), together with 16 known compounds. The structures of these new compounds were determined on the basis of their spectroscopic data. Millexatin A (1) is a rare isoflavone containing three isoprenyl units on a modified A ring. Compounds 1, 6, 10, 11, and 14 displayed promising antibacterial activity with MIC values of 2-8 µg/mL.

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.

A New Cytotoxic Clerodane Diterpene from Casearia graveolens Twigs.

The first phytochemical investigation of Casearia graveolens twigs led to the isolation and identification of a new clerodane diterpene, caseariagraveolin (1), together with six known compounds (2-7). Their structures were elucidated by intensive analysis of their spectroscopic data. Compound 1 showed strong cytotoxicity against oral cavity and breast cancer cell lines with IC50 values of 2.48 and 6.63 µM, respectively.

Xanthones from Garcinia propinqua Roots.

Phytochemical investigation of Garcinia propinqua roots led to the isolation and identification of a new xanthone, doitunggarcinone D (1), together with 15 known compounds (2-16). Their structures were elucidated by intensive analysis of spectroscopic data. Compounds 3, 6, 7, 14, 15 and 16 exhibited strong antibacterial activity against Bacillus subtilis TISTR 088 with MIC values in the range of 1-4 µg/mL. Compounds 3, 7, 10 and 14 also showed good antibacterial activity against B. cereus TISTR 688 with MIC values ranging from 4-8 µg/mL.

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.

Bioactive prenylated xanthones from the young fruits and flowers of Garcinia cowa.

Five new xanthones, garciniacowones A-E (1-5), together with 14 known xanthones, 6-19, were isolated from the young fruits and fresh flowers of Garcinia cowa. The structures of 1-5 were elucidated by analysis of their 1D and 2D NMR spectra and mass spectrometric data. The compounds 1-19 were tested in vitro for their antimicrobial activity and for their ability to inhibit α-glucosidase. Compounds 16 and 17 showed the most potent α-glucosidase inhibitory activity, with IC50 values of 7.8 ± 0.5 and 8.7 ± 0.3 µM, respectively. Compounds 8, 9, and 19 showed antibacterial activity against Bacillus subtilis TISTR 088 with identical MIC values of 2 µg/mL, while 8, 10, and 19 exhibited antibacterial activity against Bacillus cereus TISTR 688 with identical MIC values of 4 µg/mL.