Sesquiterpenoids Isolated from Two Species of the Asteriscus Alliance.

Investigation of the aerial parts of two Spanish members of the Asteriscus alliance, Asteriscus graveolens subsp. stenophyllus and Asteriscus schultzii, afforded four new sesquiterpene lactones containing a humulene skeleton (1-4) and one new sesquiterpene lactone of the asteriscanolide type (5). Their chemical structures were determined on the basis of the HRMS and from 1D and 2D NMR spectroscopic studies.

ent-Labdane Diterpenoids from the Aerial Parts of Eupatorium obtusissmum.

Six new ent-labdane diterpenoids, uasdlabdanes A-F (1-6), were isolated from the aerial parts of Eupatorium obtusissmum. The new structures were elucidated through spectroscopic and spectrometric data analyses. The absolute configurations of compounds 1 and 2 were established by X-ray crystallography, and those of 3-6, by comparison of experimental and calculated electronic circular dichroism spectra.

The eudesmanolide tanapsin from Tanacetum oshanahanii and its acetate induce cell death in human tumor cells through a mechanism dependent on reactive oxygen species.

In this study the cytotoxicities of two species of Tanacetum were evaluated against human tumor cells. Tanacetum oshanahanii extract was more cytotoxic than Tanacetum ptarmiciflorum. Analyses of both extracts of Tanacetum by ultrahigh performance liquid chromatography-tandem mass spectrometry revealed that T.

A chemotaxonomic study of endemic species of genus Tanacetum from the Canary Islands.

Aerial parts of Tanacetum oshanahanii collected at "Jardín Canario Viera y Clavijo", Tanacetum ptarmiciflorum collected at Los Moriscos (Tejeda), and Tanacetum ferulaceum var. latipinnum collected at Anden Verde (Agaete) in Gran Canaria, Canary Islands, afforded three sesquiterpenes related to nerolidol and six sesquiterpene lactones whose structures were established on the basis of their spectroscopic data and chemical transformations. In this work we show that this type of sesquiterpene lactones could be used as chemotaxonomic markers.

Secondary metabolites from two species of Tolpis and their biological activities.

Phytochemical research of two Tolpis species, T. proustii and T. lagopoda, led to the isolation of three new compounds: 30-chloro-3β-acetoxy-22α-hydroxyl-20(21)-taraxastene (1), 3β,22α-diacetoxy-30-ethoxy-20(21)-taraxastene (2) and 3β,28-dihydroxy-11α-hydroperoxy-12-ursene (3).

Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells.

Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G(2)-M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x(L). Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5.

Secondary metabolites from two species of Pulicaria and their cytotoxic activity.

Two new compounds, the sesquiterpene (1E,5E)-8β-acetoxy-4α-hydroxy-7βH-germacra-1(10),5-dien-14-oic acid (2), and a nor-sesquiterpene, (5E)-8β-acetoxy-4α-hydroxy-7βH-germacr-5-en-10-one (3), were isolated from Pulicaria canariensis ssp. lanata, along with ten known compounds, including the flavonoid 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (4). From Pulicaria burchardii, we isolated seven known compounds; the physical and spectroscopic data of the triterpenoid 3β-hydroxytaraxaster-20-en-30-al (1) are reported.

Naturally occurring asteriscunolide A induces apoptosis and activation of mitogen-activated protein kinase pathway in human tumor cell lines.

Sesquiterpene lactones have attracted much attention because they display a wide range of biological activities, including antitumor properties. Here, we show the effects of the naturally occurring sesquiterpene lactone asteriscunolide A (AS) on viability of human melanoma, leukemia and cells that overexpress antiapoptotic proteins, namely Bcl-2 and Bcl-x(L). All cell lines were sensitive to this compound, with IC(50) values of approximately 5 microM.

Chemotaxonomy of Gonospermum and related genera.

Aerial parts of Gonospermum fruticosum collected at several locations in the Canary Islands afforded, in addition to known compounds, four sesquiterpene alcohols related to costol and a sesquiterpene lactone, whose structures were established on the basis of their spectroscopic data and chemical transformations. Except for Gonospermum species collected on the island of Tenerife, those collected on the island of El Hierro and, in a previous study those from La Gomera, contain sesquiterpene lactones that can be used as chemotaxonomic markers confirming the inclusion of Gonospermum, Lugoa, and species of Tanacetum endemic to the Canary Islands in a genus that does not support the monophyly of Gonosperminae.

Betuletol 3-methyl ether induces G(2)-M phase arrest and activates the sphingomyelin and MAPK pathways in human leukemia cells.

Betuletol 3-methyl ether (BME) is a natural phenylbenzo-gamma-pyrone that inhibits cell proliferation in human tumor cell lines and induces apoptotic cell death in HL-60 cells. Here we show that BME displays strong cytotoxic properties in several human leukemia cell lines (U937, K-562, THP-1, Jurkat, and Molt-3) and in cells that over-express two anti-apoptotic proteins, namely Bcl-2 and Bcl-x(L). BME arrested HL-60 cells at G(2)-M phase of the cell cycle, which was associated with the accumulation of cyclin B1 and p21(Cip1).

Chemical constituents of Tolpis species.

Phytochemical research of two Tolpis species, T. webbii and T. sp.

Sesquiterpene lactones from Gonospermum gomerae and G. fruticosum and their cytotoxic activities.

Four new sesquiterpene lactones (1-4) and a new sesquiterpene (5) together with 20 known compounds were isolated from two Gonospermum species (G. gomerae Bolle and G. fruticosum Less).

Acetyl derivative of quercetin 3-methyl ether-induced cell death in human leukemia cells is amplified by the inhibition of ERK.

Flavonoids are polyphenolic compounds that are ubiquitously in plants and display a vast array of biological activities. Here we have studied the effect of the phenylbenzo-gamma-pyrone-derivative quercetin 3-methyl ether tetracetate (QD), obtained by acetylation of the natural product quercetin 3-methyl ether, on cell viability of human leukemia HL-60 and U937 cell lines. The results show that QD was cytotoxic and induced G2-M phase cell cycle arrest on both cell lines and it was a potent apoptotic inducer on HL-60 cells.

Phenylbenzopyrones structure-activity studies identify betuletol derivatives as potential antitumoral agents.

We have analyzed the cytotoxicity of 22 compounds with a phenylbenzo-gamma-pirone core structure, most of them obtained from natural sources, in five human tumor cell lines (HL-60, A431, SK-OV-3, HeLa and HOS). Betuletol 3-methyl ether and its diacetate were the most cytotoxic compounds. The HL-60 cell line was especially sensitive to these compounds, with IC50 values of approximately 1 microM.

Sesquiterpenoids from Pulicaria canariensis and their cytotoxic activities.

Thirteen new sesquiterpenes, pulicanadiene A (1), B (2), and C (3), pulicanone (4), pulicanol (5), pulicanarals A (6), B (7), and C (8), pulicanadienals A (9) and B (10), pulicanadienol (11), and pulioplopanones A (12) and B (13), and seven known compounds, stigmasterol, ergosterol peroxide, calenduladiol, 7,4'-di-O-methyldihydrokaempferol, 5,7-dihydroxy-3,3',4'-trimethoxyflavone, dihydroquercetin 7,3'-dimethyl ether, and 6,15alpha-epoxy-1beta,4beta-dihydroxyeudesmane, were isolated from Pulicaria canariensis. Compound 4a showed cytotoxicity on the human myeloid leukemia cell line HL-60. The cytotoxicity was caused by induction of apoptosis as determined by microscopy of nuclear changes, activation of caspases, and the cleavage of poly(ADP-ribose) polymerase-1.

Potent induction of apoptosis by germacranolide sesquiterpene lactones on human myeloid leukemia cells.

This paper studies the cytotoxic effect induced by four known natural sesquiterpene lactones (tatridin A, tamirin, reynosin, ineupatorolide A) and one synthetic derivative (tatridin A diacetate) on the myeloid leukemia cell lines HL-60 and U937. Tatridin A diacetate and ineupatorolide A were found to be the most cytotoxic compounds with growth inhibition caused by induction of apoptosis as determined by flow cytometry and microscopy of nuclear changes. The results reported here support the conclusion that apoptosis was accompanied by both the activation of caspase-3 and the fragmentation of poly(ADP-ribose) polymerase-1 and was also associated with an early release of cytochrome c from the mitochondria.

Sesquiterpenoid derivatives from Gonospermum elegans and their cytotoxic activity for HL-60 human promyelocytic cells.

Four new compounds, a sesquiterpene, eleganodiol (1), and three sesquiterpene lactones, eleganolactone A (2), eleganolactone B (3), and elegain (4), were isolated from Gonospermum elegans along with 16 known compounds. The structures of 1, 2, and 4 were determined on the basis of MS and NMR studies of their acetate derivatives (1a, 2a, 4a). The structure of the acetate derivative (3a) of 3 was determined on the basis of spectroscopic data interpretation and by single-crystal X-ray diffraction.