New sesquiterpene lactones from Inula species

An investigation of Inula helenium, I. royleana, I. salicina and I. bifrons afforded in addition to known sesquiterpene lactones 20 new lactones, the eudesmanolides 3, 6 and 8–12, the germacranolides 14–18 and 20–22, the guaianolides 23 and 25, the pseudoguaianolide 26, the xanthanolides 28 and 32 and the cyclopropane analogue 30. Structures and configurations of these new compounds were established by extensive PMR studies and by some chemical transformations. Some of the investigated species contain besides the widely distributed pentaynene 33 several known thymol derivatives together with a new one (40).     

New sesquiterpene lactones from Inula oculus-christi L.

Investigation of the aerial parts of Inula oculus-christi L. led to the identification of four new sesquiterpene lactones: an eudesmanolide (4α,15α-epoxypulchellin E) and three guaianolides (2α-acetoxy-4α,9β-dihydroxy-1β-guaia-11(13),10(14)-dien-12,8α-olide, 9β,10β-epoxygaillardin, 9α,10α-epoxy-2-epi-gaillardin), in addition to the known gaillardin, pulchellin E, pulchellin C and 3-O-palmitates of 16β-hydroxylupeol, 16β-hydroxy-β-amyrin, and faradiol. The structures of all compounds have been elucidated on the basis of their spectral data.     

Cytotoxic sesquiterpene lactones from Artemisia anomala

Two new sesquiterpene lactones, 8α-acetoxy-1,10α-epoxy-2-oxo-guaia-3,11(13)-dien-12,6α-olide (1) and 13-acetoxy-1-oxo-4α-hydroxy-eudesman-2(11)-dien-12,6α-olide (2), along with six known analogs (3-8), were isolated from the whole plant of Artemisia anomala S. Moore. Their structures were elucidated by extensive analysis of spectroscopic data. Compounds 6 and 7 exhibited in vitro moderate cytotoxicity against A549 cells with IC₅₀ values of 0.6 and 0.9 μM, and HepG2 cells with IC₅₀ values of 5.4 and 3.0 μM, respectively.     

Cytotoxic activity of some lichen extracts on murine and human cancer cell lines

Eight lichens were extracted successively with n-hexane, diethyl ether and methanol using a Soxhlet process. The cytotoxic activity of the 24 lichen extracts was evaluated in vitro using two murine (the L1210: lymphocytic leukaemia, and the 3LL: Lewis lung carcinoma) and four human (the K-562: chronic myelogenous leukaemia, the U251: glioblastoma, the DU145: prostate carcinoma, and the MCF7: breast adenocarcinoma) cancer cell lines and non-cancerous cells, the Vero cell line (African green monkey kidney cell line). The MTT assay revealed significant cytotoxicity (IC50 < or = 20 microg/ml) on one of the tested cancer cell lines for at least one extract of each lichen species. Some extracts of Cladonia convoluta, Cladonia rangiformis, Parmelia caperata, Platismatia glauca and Ramalina cuspidata demonstrated interesting activities particularly on human cancer cell lines as good selectivity indices were recorded (SI > 3).     

Antifungal activity of sesquiterpene lactones

Forty-five sesquiterpene lactones were screened for their antifungal activities against Microsporum cookei, Trichophyton mentagrophytes and Fusarium sp. The screening tests showed that a majority of sesquiterpene examined possess at least weak antifungal activity, the eudesmanolides being the most active. The antifungal activity of sesquiterpene lactones cannot be explained by the presence or absence of two potential active sites (the exocyclic methylene and, in pseudoguaianolides, a β-unsubstituted cyclopentenonel) but other functions must play a role in enhancing or reducing this activity.     

Sesquiterpene lactones from Inula cappa

Three new germacranolides, ineupatolides A–C (1–3), together with six known sesquiterpenoids, were isolated from the aerial parts of Inula cappa (Buch.-Ham.) DC. The structures of new compounds were elucidated by 1D-, and 2D-NMR techniques including HMQC, HMBC, ¹H–¹H COSY and ROESY spectra. The known compounds were identified by spectroscopic data analyses and data comparison. Compound 2 was finally proved to be converted from 1 with the trace existence of acid. Compounds 2 and 5 showed moderate inhibitory activity against human leukemia cell line HL-60, while compounds 2, 5, 6, 7 and 9 exhibited no antiproliferative activities on human lung cancer cell line A549.     

Composition and bioactivity of polysaccharides from Inula britannica flower

In this paper, the composition and biological activities of polysaccharides from Inula britannica flower IBP obtained by water extraction were investigated. The properties and chemical compositions of IBP were analyzed with HPLC and IR methods. The results showed that IBP consisted of two kinds of polysaccharides with the molecular weight of 3500Da, 700Da. IBP consisted of mannose, glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, arabinose with a molar ratio of 4.1:1:1.4:2.7:14.6:6.3:7.9. The IR spectrum of IBP revealed the typical characteristics of polysaccharides and protein. IBP was administered orally at three doses [100, 200 and 400mg/kg body weight] for 14 days to the diabetic mice induced by alloxan. The body weight, plasma glucose, serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and liver glycogen were evaluated in normal and alloxan-induced diabetic mice. IBP could dose-dependently significantly increase the body weight of diabetic mice, and reverse the decrease of plasma glucose, glycogen and the decrease of blood lipid of diabetic mice as compared to those in control group. These results indicated that IBP could be developed to a potential anti-diabetic drug in the future.     

Triterpene fatty acid esters and flavonoids from Inula britannica

Two new triterpene fatty acid esters, 3β,16β-dihydroxylupeol 3-palmitate and 3β,16β-dihydroxylupeol 3-myristate, and a new kaempferol derivativ     

Sesquiterpene lactones from Inula montana L

Aerial parts of Inula montana were investigated for its sesquiterpenoid composition. Five sesquiterpene lactones, isoinuviscolide, gaillardin, 1beta-hydroxy-3beta-acetoxy-eudesm-4(15), 11(13)-dien-12-8beta-olide, pulchellin-C and pulchellin-E were identified for the first time in this plant. One of them, 1beta-hydroxy-3beta-acetoxy-eudesm-4(15),11(13)-dien-1 2-8beta-olide, is a novel natural product. The structures of this compounds were established by 1D and 2D-NMR spectroscopy.     

Cytotoxic activity of some marine brown algae against cancer cell lines

The aim of this study was to investigate the in vitro cytotoxic activity of total extract of MeOH (70%) and partition fractions of hexan, chloroform (CHCL3), ethylacetate (EtOAc) and MeOH-H2O of brown algae species (Sargassum swartzii, Cystoseira myrica, Colpomenia sinuosa) found in the Persian Gulf against in different cell lines including HT-29, Caco-2, T47D, MDA-MB468 and NIH 3T3 cell lines by MTT and AnnexinV-PI assay. The hexan fraction of S. swartzii and C. myrica showed selective cytotoxicity against proliferation of Caco-2 cells (IC50 < 100 μg/ml) T47D cell line (IC50<100 μg/ml), respectively. S. swartzii and C. myrica were also observed for increasing apoptosis in Caco-2 and T47D cells. Total extract and fractions of C. sinuosa did not show any significant cytotoxicity against the studied cell lines. MDA-MB468 cells were more sensitive to C. myrica than was T47D (IC50 99.9 ± 8.11 vs. 56.50' ± 0.88). This reflects an estrogen receptor independent mechanism for cytotoxicity of the extract. The IC50 of the hexan fraction of C. myrica on T47D parent cells was lower than it was on T47D-TR cells (IC50 99.9 ± 8.11 vs. 143.15 ± 7.80). This finding suggests a role for the MDR-1 in the development of possible future tolerance to the extract.     

Cytotoxic effect of 2,3-disubstituted chromanones in human cancer cell lines

Four different synthetic compounds [3-aryl-2-(3-pyridyl)chromanones] were prepared and screened for cytotoxicity against a panel of 29 human cancer cell lines in five different concentrations separately. All compounds displayed cytotoxicity against cancer cell lines and one of them possessed cell type selectivity also.     

Cytotoxic effects of digalloyl dimer procyanidins in human cancer cell lines

Flavanols, a class of polyphenols present in certain plant-based foods, have received increasing attention for their putative anticancer activity. In vitro and in vivo studies, which have compared the effectiveness of various monomer flavanols, indicate that the presence of a galloyl residue on the 3 position on the C-ring enhances the cytotoxicity of these compounds. Procyanidins, oligomerized flavanols, have been reported to be more cytotoxic than monomer flavanols in a variety of human cancer cell lines. Given the above, we evaluated the potential anticancer properties of dimer procyanidins that contain galloyl groups. Specifically, the cytotoxicity of synthetic digalloyl dimer B1 and B2 esters {[3-O-galloyl]-(−)-epicatechin-(4β,8)-(+)-catechin-3-O-gallate (DGB1) and [3-O-galloyl]-(−)-epicatechin-(4β,8)-(+)-epicatechin-3-O-gallate (DGB2), respectively} were tested in a number of in vitro models. DGB1 produced significant cytotoxicity in a number of human cancer cell lines evaluated by three independent methods: ATP content, MTT and MTS assays. For the three most sensitive cell lines, exposure to DGB1 and DGB2 for 24, 48 or 72 h was associated with a reduction in cell number and an inhibition of cell proliferation. Digalloyl dimers exerted significantly higher cytotoxic effects than the structurally related flavanols, (−)-epicatechin, (+)-catechin, (−)-epicatechin gallate, (−)-epigallocatechin gallate, (−)-catechin gallate and dimer B1 and B2. These results support the concept that the incorporation of galloyl groups and the oligomerization of flavanols enhances the cytotoxic effects of typical monomer flavanols. The therapeutic value of these compounds and their derivative forms as anticancer agents merits further investigation in whole animal models.     

Cytotoxic activity of a recombinant GnRH-PAP fusion toxin on human tumor cell lines

Pokeweed antiviral protein (PAP), a ribosome-inactivating protein isolated from the leaves of Phytolacca americana, reveals potent antiviral activity against viruses or cytotoxic action against cells once inside the cytoplasm. Therefore PAP is a good candidate to be used as an immunotoxin. We constructed a bacterial expression plasmid encoding PAP as a fusion protein with gonadotropin-releasing hormone (GnRH), a neuropeptide with receptor sites on several gynaecologic tumors. The resulting recombinant toxin was produced in Escherichia coli and accumulated in inclusion bodies. After purification under denaturing conditions, renaturated GnRH-PAP shows an IC(50) of 3 nM on in vitro translation assays and selectively inhibits the growth of the GnRH receptor positive Ishikawa cell line (ID(50) of 15 nM); on the other hand, neither GnRH nor PAP alone had any effect.     

Flavonoids of Inula britannica protect cultured cortical cells from necrotic cell death induced by glutamate

We previously reported 12 antioxidative flavonoids isolated from the n-BuOH extract of Inula britannica (Asteraceae). This prompted us to investigate further whether these flavonoids also showed antioxidative activity upon live cells grown in a culture system. Among the 12 flavonoids tested, only patuletin, nepetin, and axillarin protected primary cultures of rat cortical cells from oxidative stress induced by glutamate. These flavonoids exerted significant neuroprotective activity when they were administered either before or after the glutamate insult. Treatment with these flavonoids maintained the activities of such antioxidant enzymes as catalase, glutathione-peroxidase, and glutathione reductase, all of which play important roles in the antioxidative defense mechanism. Moreover, these three flavonoids also attenuated significant drops in glutathione induced by glutamate which is a routine concomitant of oxidative stress by inhibiting glutathione diminution. Accordingly, these flavonoids did not stimulate the synthesis of glutathione. With regard to structure-activity relationships, our results indicated that the 6-methoxyl group in the A ring and the 3', 4'-hydroxyl groups in the B ring are crucial for the protection against the oxidative stress; glycosylation greatly reduced their protective activities. Collectively, these results indicated that patuletin, nepetin, and axillarin strongly protect primary cultured neurons against glutamate-induced oxidative stress.     

Deterrent activity of sesquiterpene lactones from the umbelliferae against storage pests

The deterrent activity of eight native sesquiterpene lactones isolated from the species Laserpitium siler L., L. archangelica Wulf. and Laser trilobum (L.) Borkh. and one synthetically prepared lactone have been tested against selected storage pest insects. All nine lactones under investigation showed deterrent activity differing according to their structure.     

Two guaiane-type sesquiterpene lactones and their related sesquiterpene lactones from Porella japonica

Two new guaiane-type sesquiterpene dilactones, porelladiolide and 3α,4α-epoxyporelladiolide and a new germacranolide, 3β-hydroxycostunolide, together with the previously known germacranolides, guaianolides, pinguisane-type sesquiterpenes, and a sacculatane-type diterpene dialdehyde have been isolated from the liverwort, Porella japonica and their structures have been established by the spectral evidence and some chemical transformations. Porelladiolide, 3α,4α-epoxyporelladiolide and the sesquiterpene with α-methylene γ-lactone group showed inhibitory activity toward the germination and growth of roots of rice in the husk.     

Sesquiterpene lactones from the aerial parts of Xanthium sibiricum and their cytotoxic effects on human cancer cell lines

The EtOH extract of the aerial parts of Xanthium sibiricum afforded six sesquiterpene lactones (STLs), including two new eremophilanolides. The structures of the new compounds were established on the basis of spectroscopic methods and the modified Mosher's method to be the C-11 epimers of 2S,4S,5R,7R,8R-2-hydroxy-eremophil-1(10)-en-12,8-olide [11R: 1 (sibiriolide C); 11S: 2 (sibiriolide D)]. The isolated compounds were evaluated for their in vitro cytotoxicities against five human cancer cell lines (Huh-7 hepatocarcinoma, KB nasopharynx carcinoma, Jurkat T cell lymphoblast, BGC-823 and KE-97 gastric carcinoma) using the CellTiter-Glo? luminescent cell viability assay method. Compounds 4–6, each possessing an α-methylene-γ-lactone moiety, were found to have noteworthy cytotoxic effects with IC₅₀ values ranging from 1.1 to 18.0 μM.     

Two sesquiterpene lactones from Abutilon indicum

Abutilon indicum afforded two sesquiterpene lactones identified as alantolactone and isoalantolactone. This is the first report of the occurrence of these compounds in the genus Abutilon and in the family Malvaceae.     

New sesquiterpene lactones from Liriodendron tulipifera

Four new sesquiterpene lactones were obtained from L. tulipifera; two germacranolides, lipiferolide (4) and epitulipinolide diepoxide (5) from the leaves, an elemanolide, epitulipdienolide (7), and an eudesmanolide, γ-liriodenolide (6) from the root bark. Structural determination was by physical and chemical methods and by direct correlation to the known epitulipinolide (3). Lipiferolide and epitulipinolide diepoxide possess cytotoxic activity against KB cells.     

Further sesquiterpene lactones from Helianthus maximiliani

By using HPLC, a new melampolide, a known heliangolide and three known germacrolides were isolated as minor constituents from a north central Texas population of Helianthus maximiliani. In an earlier report, we identified the germacrolide desacetyleupaserrin as the principal sesquiterpene lactone from this population.