Novel cytotoxic icetexane diterpenes from Premna latifolia Roxb

Chromatographic fractionation of a hexane extract from stem-bark of Premna latifolia yielded three new icetexane diterpenes (1-3). Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS, data. Compounds 1-3 were also evaluated for the cytotoxicity against the cancer cell lines (HT-29, A-431, MCF-7, Hep-G2, PC-3, A-549, B-16 F10 and ACHN). Compounds 1 and 2 displayed potent cytotoxic activity against HT-29 and Hep-G2 cell lines with IC₅₀ values of 0.04 and 0.18 μg/mL, respectively.     

Cytotoxic bromoditerpenes from the red alga Sphaerococcus coronopifolius

Three new brominated diterpenes (1, 2, 8), along with six previously reported metabolites (3-7, 9), were isolated from the organic extract of Sphaerococcus coronopifolius, collected in Palaiokastritsa bay at the west coasts of Corfu Island. The structures of the new natural products, as well as their relative stereochemistry, were established by means of spectral data analyses, including 2D experiments. The absolute stereochemistry of 2 and 4 as well as the structure revision of the previously reported metabolite 3 were established by X-ray crystallographic analyses. The cytotoxicity of the isolated metabolites was evaluated against the NSCLC-N6-L16 and A549 human lung cancer cell lines.     

Identification of anti-inflammatory diterpenes from the marine gorgonian Pseudopterogorgia elisabethae

Analysis of the terpene metabolites of Pseudopterogorgia elisabethae collected from the Florida Keys has resulted in the identification of a novel hydroxyquinone, elisabethadione (1), as well as new pseudopterosins and seco-pseudopterosins. Anti-inflammatory assays indicate that elisabethadione is more potent than the well characterized pseudopterosin A and E. This report also describes the co-occurrence of pseudopterosins and seco-pseudopterosins, diterpenes with amphilectane and serrulatane skeletons, respectively. This together with our previously described isolation of elisabethatriene as the sole diterpene cyclase product in P. elisabethae suggests that the amphilectane and serrulatane families of diterpenes are derived from the same geranylgeranyl diphosphate cyclase product.     

New tri- and tetracyclic diterpenes from Euphorbia villosa

Three new tetracyclic diterpenes were isolated from the chloroform-soluble extract of Euphorbia villosa, together with one new and one known lathyrane diterpene. The structures were elucidated by means of various spectroscopic methods, including HREI-MS, HRFAB-MS, UV, and 1D and 2D NMR techniques. Spectral analyses revealed that two of the tetracyclic compounds contain the rare 5-6-6-4 fused ring system, while the third has a 5-6-7-3 fused diterpene core. Such diterpene skeletons have previously been found only in euphoractines A-E isolated from Euphorbia micractina. As a new structural feature, the diterpene framework described here has a C-2 epimer configuration. The new lathyrane diterpene is a diester of a hitherto unknown polyfunctional parent alcohol.     

Novel taxoids from the Chinese yew Taxus yunnanensis

Six new taxoids, taxuyunnanines W (1), X (2), Y (3), Z (5), 10-deacetyl-10-(β-glucopyranosyl)-yunnanxane (8), and 7-(β-xylosyl)-N-methyl-taxol C (10), as well as taxuchin B (4) and yunnanxane (7), have been isolated from the bark of Taxus yunnanensis. Compounds 1 and 2 were characterized as 11(15→1)-abeo taxoids containing an orthoester group, which have not been reported from any Taxus plants to date; isolates 3 and 5 are the examples of taxanes having a tetrahydronfuran ring, being reported only for the second time; and 8 is the first natural 6/8/6 skeletal type taxane glucosidic form. This is also the first report of a co-occurrence of xylosidation and N-methylation in a taxane (10). Compound 4 is the only known chlorine-containing taxane found in nature thus far, and is being reported from this plant for the first time. The structures were determined by spectroscopic and chemical means including 1D and 2D NMR spectra.     

A novel 3,8-seco-taxane metabolite from the seeds of the Chinese yew, Taxus mairei

The structure of a novel 3,8-seco-bicyclic taxanoid metabolite, isolated from the methanol extract of seeds of the Chinese yew, Taxus mairei, was established as (11αH)-3,8-seco-taxa-3E,7E,12(18)-triene-2α,6α,9β-triol (1) on the basis of spectral analysis including ¹H NMR, ¹³C NMR, HMQC, HMBC, NOESY and HR-FABMS.     

Novel routes for the generation of structurally diverse labdane diterpenes from andrographolide

Andrographolide 1, the major constituent of the Indian medicinal plant Andrographis paniculata (Acanthaceae) was converted into the key intermediate 4 by selective oxidative degradation of the C-12,13 olefin bond. The aldehyde functional group present in 4 has been utilized for synthesizing a number of structurally diverse labdane diterpenes. Synthesis and in vitro cytotoxic activity results of the compounds prepared are discussed.     

Premnalatifolin A, a novel dimeric diterpene from Premna latifolia Roxb

Premnalatifolin A (1), a unique icetexane diterpene dimer was isolated from the stem-bark of Indian medicinal plant, Premna latifolia. Its structure and relative stereochemistry were elucidated on the basis of detailed spectroscopic analysis, including HRESIMS and 2D NMR (COSY, HSQC, HMBC, and NOESY) spectra. The compound has dimeric carbon skeleton composed of two icetexane skeletal diterpenes linked via ether bond. Further, premnalatifolin A (1) was also evaluated for its cytotoxicity against cancer cell lines (HT-29, A-431, MCF-7, Hep-G2, PC-3, A-549, B-16 F10, and ACHN), which displayed potent activity against HT-29 and MCF-7 cell lines with the IC₅₀ values of 12.15 and 1.11 μg/mL, respectively.     

New cytotoxic sesquiterpenes from the red algae Laurencia obtusa and Laurencia microcladia

Three new sesquiterpenes (1-3), along with five known (5-9), were isolated from the organic extract of the red alga Laurencia obtusa, collected from the coastal rocks of Serifos in the Aegean Sea. A new dimeric sesquiterpene of the cyclolaurane-type (4) along with four previously reported (7, 10-12) metabolites, were isolated from the extract of Laurencia microcladia, collected at Chios island in the North Aegean Sea. The structures and the relative stereochemistry of the compounds are proposed on the basis of their spectral data. The cytotoxicity of the isolated metabolites was evaluated against several cell lines including human tumor cell lines.     

New sesquiterpenes from the red alga Laurencia microcladia

Three new aromatic sesquiterpenes (1, 2, and 4), one new dimeric sesquiterpene of the cyclolaurane-type (3), one sesquiterpene alcohol of bisabolene type (8) along with three previously reported metabolites (5-7), were isolated from the organic extracts of Laurencia microcladia, collected from the Chios island in the North Aegean Sea. The structures of the new natural products, as well as their relative stereochemistries, were established by means of spectral data analyses, including 2D experiments. The cytotoxicity of the isolated metabolites was evaluated against five human tumor cell lines.     

Novel cytotoxic kaurane-type diterpenoids from the New Zealand Liverwort Jungermannia species

Novel cytotoxic rearranged kaurene- and ent-kaurene-type diterpenoids against HL-60 cells have been isolated from the unidentified New Zealand liverwort Jungermannia species together with previously known ent-kaurane-type diterpenoids. Their structures were determined by extensive NMR techniques, chemical degradation and X-ray crystallographic analysis.     

Structural and spectroscopic characteristics of two new dibenzylbutane type lignans from Taxus baccata L.

Chromatographic separation of chloroform extracts of the heartwood of Taxus baccata L. has yielded two new dibenzylbutane type lignans, together with a known lignan. Their structures were established as 3′-demethylisolariciresinol-9′-hydroxy isopropylether (1) and 3-demethylisolariciresinol (2) and isolariciresinol (3) on the basis of 1D- and 2D-NMR spectroscopic analysis. Compounds 1 and 2 were identified as new lignans of isolariciresinol derivatives. Compound 1 is the first lignan with a hydroxyisopropyl group at C-9′. Molecular mechanic calculations of these compounds were carried out by using mm3 program. Furthermore, the conformations of these three compounds were computed with the semi-empirical molecular orbital methods AM1 and PM3 by using X-ray crystal structure results of similar compounds. So, three-dimensional, the most probable structure of these compounds were obtained, compared and discussed.     

Eight new diterpenoids from soft coral Cespitularia hypotentaculata

Chemical investigation of the soft coral Cespitularia hypotentaculata resulted in the isolation of eight new diterpenes, cespihypotins E-L (1-8). The new metabolites comprise of six verticillene-type diterpenes, one cespitularane derivative, and one derivative with 14-membered lactone ring. The structures were determined through detailed spectroscopic analyses, especially high resolution ESIMS and 2D NMR techniques. The relative stereochemistry was deduced from NOESY spectrum and application of Mosher's ester technique. Immunomodulatory and antiviral activities of 1-8 were tested and evaluated. The biogenetic pathways for 1-8 were also proposed.     

Unusual cycloartane glycosides from Astragalus eremophilus

Eleven new cycloartane-type glycosides, named eremophilosides A-K have been isolated from the aerial parts of Astragalus eremophilus. Their structures were elucidated by MS and NMR experiments and the relative configurational analysis of eremophilosides C and D was carried out on the basis of the recently reported J-based method. Additionally, the cytotoxic activity of these compounds in MCF7 and U937 cell lines was evaluated. All tested compounds, except eremophilosides B, C, and J were found to inhibit slightly the growth (controlling the cell cycle) and/or to induce death processes in U937 cell line, the most susceptible cell line. Eremophilosides A and K resulted the most effective to induce cell death, the first by necrosis while the latter by apoptosis.     

New diterpenes of the pseudopterane class from two closely related Pseudopterogorgia species: isolation, structural elucidation, and biological evaluation

Parallel chemical investigations of the hexane and chloroform extracts of the sea plumes Pseudopterogorgia bipinnata and Pseudopterogorgia kallos has led to the discovery of seven new diterpenoids of the pseudopterane class, namely, kallolide D (2), kallolide C acetate (3), kallolide E (4), kallolide F (5), kallolide G (6), kallolide H (7), and kallolide I (8), in addition to nine previously described compounds of the pseudopterane and gersolane families of diterpenes. The chemical structures of the new metabolites were established by 1D and 2D NMR, IR, UV, HRMS, and, in some instances, by single-crystal X-ray crystallographic analyses. Biological screening of these metabolites revealed significant anti-parasitic activity albeit marginal anti-tubercular activity.     

Bioactive pregnane-type steroids from the soft coral Scleronephthya gracillimum

Nine new steroids, sclerosteroids A-I (1, 5, 6, 8-13), along with 18 known metabolites (2-4, 7, 14-27), were isolated from the soft coral Scleronephthya gracillimum. These structures were elucidated on the basis of detailed spectroscopic analysis. The absolute configurations of sugar moieties in steroidal glycosides 10-13 were determined by HPLC analysis of the o-tolylthiocarbamate derivatives of the liberated sugars from hydrolysis of these steroidal giycosides. Cytotoxic and anti-inflammatory activities of these compounds were measured in vitro.     

Polyketides from the mangrove-derived endophytic fungus Acremonium strictum

Five new polyketide derivatives, 6′-hydroxypestalotiopsone C (1), acropyrone (2), bicytosporone D (3), waol acid (4), and pestalotiopene C (5), together with seven known metabolites (6–12), were obtained from extracts of the endophytic fungus Acremonium strictum, isolated from the mangrove tree Rhizophora apiculata. The structures of the isolated compounds were elucidated on the basis of comprehensive NMR and MS analysis. Compounds 6, 7, and 9 showed moderate cytotoxic activity against human cisplatin-sensitive (IC₅₀ values 27.1, 76.2, and 8.3 μM, respectively) and resistant A2780 cell lines (IC₅₀ values 12.6, 30.1, and 19.0 μM, respectively), whereas only 9 exhibited antibacterial activity against Staphylococcus aureus (MIC value 14.3 μM).     

Cytotoxic cuparene sesquiterpenes from Laurencia microcladia

Three new cuparene sesquiterpenes 1-3 were isolated from the organic extract of the red alga Laurencia microcladia, collected at Chios island in the North Aegean Sea, Greece. The structures and the relative stereochemistry of the compounds are proposed on the basis of their spectral data. Metabolite 2 shows an unprecedented (for the cuparene class of sesquiterpenes) migration of the C-1 methyl group. All metabolites 1-3 were found to exhibit significant cytotoxic activity against two lung cancer cell lines.     

Bioactive prenylated xanthones and anthraquinones from Cratoxylum formosum ssp. pruniflorum

Ten new compounds (1-10), pruniflorone A-J, together with 21 known compounds (11-31) were isolated from the roots and barks of Cratoxylum formosum ssp. pruniflorum. Their structures were determined by spectroscopic methods. Compounds 1 and 11 were also confirmed by X-ray diffraction data. In addition, antibacterial and cytotoxic activities of the isolates were also evaluated.     

Novel sesquiterpenes and norergosterol from the soft corals Nephthea erecta and Nephtheachabroli

Chemical investigations on the acetone extract of the Formosan soft coral Nephthea erecta have afforded a new calamenene-type sesquiterpene with a mercaptan group at C-15, erectathiol (1), and a previously reported sesquiterpenoid, (+)-trans-calamenene (2). A novel sec-germacrane sesquiterpene (3), along with a novel norergosterol, chabrosterol (4), possessing a 19-norergostane skeleton, was isolated from the other soft coral Nephthea chabroli. The structures of these metabolites were elucidated through extensive spectroscopic analyses. In vitro anti-inflammatory activity of 1 and 4 (10 μM) significantly reduced the levels of the iNOS protein (58.0 ± 6.5% and 12.4 ± 2.9%) and COX-2 protein (108.7 ± 4.5% and 45.2 ± 5.4%). In addition, metabolite 1 (166 μg/disk) exhibited antimicrobial activities against a small panel of bacterial strains.