Secondary metabolites from Senecio burtonii (Compositae)

A cacalolide derivative named 4alpha-[2'-hydroxymethylacryloxy]-1beta-hydroxy-14-(5-->6) abeo eremophilan-12,8-olide and a shikimic acid derivative named (3'E)-(1alpha)-3-hydroxymethyl-4beta,5alpha-dimethoxycyclohex-2-enyloctadec-3'-enoate along with three known compounds, octacosan-1-ol, 3beta-hydroxyolean-12-en-28-oic acid and 3beta-acetoxyolean-12-en-28-oic acid were isolated from Senecio burtonii. Their structures and relative configurations were established on the basis of spectroscopic analysis.     

Guaianolide sesquiterpenes from Pulicaria crispa (Forssk.) Oliv

A phytochemical study of the asteraceous herb Pulicaria crispa (Forssk.) Oliv. resulted in the characterisation of three guaianolide sesquiterpenes, 2alpha,4alpha-dihydroxy-7alphaH,8alphaH,10alphaH-guaia-1(5),11(13)-dien-8beta,12-olide (1), 1alpha,2alpha-epoxy-4beta-hydroxy-5alphaH,7alphaH,8alphaH,10alphaH-guaia-11(13)-en-8beta,12-olide (2) and 5,10-epi-2,3-dihydroaromatin (3). The structures were assigned on the basis of extensive 1 and 2D NMR experiments. Compound 3 exhibited weak antimycobacterial activity against Mycobacterium phlei with a minimum inhibitory concentration of 0.52 mM and cytotoxicity (IC50 of 5.8+/-0.2 microM) in a human bladder carcinoma cell line, EJ-138.     

Diterpenoids and triterpenoids from Euphorbia guyoniana

Two new compounds with tigliane and cycloartane skeletons: 4,12-dideoxy(4alpha)phorbol-13-hexadecanoate (1) and 24-methylenecycloartane-3,28-diol (2), respectively, in addition of four known diterpenoids and 13 triterpenoids: 3-benzoyloxy-5,15-diacetoxy-9,14-dioxojatropha-6(17),11-diene (4), ent-abieta-8(14),13(15)-dien-16,12-olide (5), ent-8alpha,14alpha-epoxyabieta-11,13(15)-dien-16,12-olide (6), ent-3-hydroxyatis-16(17)-ene-2,14-dione (7), 3beta-hydroxytaraxer-14-en-28-oic acid (8), beta-sitosteryl-3beta-glucopyranoside-6'-O-palmitate (9), multiflorenyl acetate (10), multiflorenyl palmitate (11), peplusol (12), 24-methylenecycloartanol (3), lanosterol (13), euferol (14), butyrospermol (15), cycloartenol (16), obtusifoliol (17), cycloeucalenol (18) and beta-sitosterol (19), were isolated from the roots of Euphorbia guyoniana. Their structures were established on the basis of physical and spectroscopic analysis, including 1D and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY) and by comparison with the literature data.     

Three labdane diterpenoids from Aframomum sceptrum (Zingiberaceae)

Three labdane diterpenoids, 8beta,17-epoxy-3beta,7beta-dihydroxy-12(E)-labden-16,15-olide (1), methyl 8beta,17-epoxy-3beta,7beta,15-trihydroxy-12(E)-labden-16-oate (2) and 3beta,7beta,8beta,12zeta,17-pentahydroxylabdan-16,15-olide (3) have been isolated from the seeds of Afromomum sceptrum K. Schum (Zingiberaceae) and their structures assigned on the basis of their spectroscopic properties. Nerolidol, and the known flavonoids 3-acetoxy-4',5,7-trihydroxyflavanone, and 3,4',5,7-tetrahydroxyflavanone were also obtained.     

neo-Clerodane diterpenoids from Baccharis flabellata

Three diterpenoid derivatives were isolated from the acetone extract of Baccharis flabellata. Their structures were elucidated as 2,19;15,16-diepoxy-neo-clerodan-3,13(16),14-trien-18-oic acid, 15,16-epoxy-5,10-seco-clerodan-1(10),2,4,13(16),14-pentaen-18,19-olide and 15,16-epoxy-neo-clerodan-1,3,13(16),14-tetraen-18,19-olide through spectroscopic analyses.     

Diterpenes from Alomia myriadenia (Asteraceae) with cytotoxic and trypanocidal activity

Further investigation of the aerial parts of Alomia myriadenia revealed an halimane diterpene identified as ent-8S,12S-epoxy-7R,16-dihydroxyhalima-5(10),13-dien-15,16-olide along with the known ent-16-hydroxylabda-7,13-dien-15,16-olide, ent-12R-hydroxylabda-7,13-dien-15,16-olide, 6,7-methylenedioxycoumarin (ayapin), and kaempferol-7-methylether (rhamnocitrin). Evaluated in a panel of human cancer cell lines, the 16-hydroxylabade diterpene was the most active, showing an ED(50) value of 0.3 mug/ml against Lu1 (human lung cancer) cells. Tested in vitro against Trypanosoma cruzi in infected murine blood, this compound caused lysis of 100% of the parasites at 250 mug/ml.     

Terpenoids from Tripterygium doianum (Celastraceae)

The extract of Tripterygium doianum (Celastraceae) afforded three triterpenoids [3beta-acetoxy-11-ursen-13alpha,30-olide, 25-chloro-24-hydroxytirucall-7-en-3-one and tirucall-7-en-3,24-dione], two sesquiterpenoids [5alpha-acetoxy-1beta,8alpha-bis-cinnamoyl-4alpha-hydroxydihydroagarofuran and 5alpha-acetoxy-1beta-benzoyl-8alpha-cinnamoyl-4alpha-hydroxydihydroagarofuran] and nine known triterpenoids. Their structures were established based on spectroscopic studies.     

Isolation of an alpha-methylene-gamma-butyrolactone derivative, a toxin from the plant pathogen Lasiodiplodia theobromae

Lasiodiplodia theobromae is known as a multi-infectious microorganism that causes considerable crop damage, particularly to tropical fruits. When the fruits are infected by L. theobromae, the typical symptom is the appearance of black spots on the surface of the infected fruit. When injected in to the peel of banana, the culture filtrate of L. theobromae induced formation of black spots. The structure of the isolated compound responsible for this effect was determined to be (3S,4R)-3-carboxy-2-methylene-heptan-4-olide on the basis of analysis of MS, IR, and 1H and 13C NMR spectroscopic data, including HMQC, HMBC, and 1H-1H COSY experiments. The active compound was not only isolated from the culture filtrate derived from potato dextrose medium, but also from the extract of infected peels of bananas.     

Alisolide, alisols O and P from the rhizome of Alisma orientale

A nor-protostane, alisolide (1), a rearranged protostane, alisol O (2), and a 2,3-seco-protostane triterpene, alisol P (3), were isolated from the rhizomes of Alisma orientale, along with eight known protostane triterpenes. The structures were elucidated to be (17S)-3,11-dioxo-23-nor-protost-12-en-23(17)-olide, 3-oxo-11beta,23-dihydroxy-24,24-dimethyl-26,27-dinorprotost-13(17)-en-25-oic acid, and (20R,23S,24R)-23,24,25-trihydroxy-2,3-seco-protost-13(17)-en-3-oic acid 2,11beta-lactone, respectively, by interpretation of spectroscopic data.     

New triterpenoid saponins from Patrinia scabiosaefolia

Phytochemical investigation of the methanol extract from the whole plants of Patrinia scabiosaefolia Fisch. resulted in the isolation of four new triterpenoid saponins (1–4) along with six known compounds (5–10). On the basis of spectroscopic and chemical methods, the structures of the new compounds were established as 3-O-β-d-xylopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-12β,30-dihydroxy-olean-28,13β-olide (1), 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-12β,30-dihydroxy-olean-28,13β-olide (2), 3-O-β-d-xylopyranosyl-(1→2)-β-d-glucopyranosyl-12β, 30-dihydroxy-olean-28,13β-olide (3), and 3-O-β-d-glucopyranosyl-(1→4)-β-d-xylopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-oleanolic acid 28-O-β-d-glucopyranoside (4), respectively. Compounds 1–3 possess a novel 12β,30-dihydroxy-olean-28,13β-lactone aglycone and a 12β-hydroxy substituent that is rarely found in this kind of triterpenoid saponin.     

Cytotoxic sesquiterpenes from Ligularia platyglossa

Four sesquiterpene lactones including an eremophilenolide dimer, named as biligulaplenolide, 1, 8beta-hydroxy-1-oxo-(14alpha,15alpha eremophil-7(11),9(10)-dien-12,8alpha-olide, 2, 1-hydroxy-2-oxo-(14alpha,15alpha eremophil-1(10),7(11),8(9)-trien-12,8-olide, 3, 4alpha,8beta,9alpha-trihydroxy- 5alphaEta-7(11)-eudesmen-12,8alpha-olide, 4, along with two known ones, 10alpha-hydroxy-1-oxo-eremophil-7(11),8(9)-dien-12,8-olide, 5, and furanoeremophil-1(10)-ene-2,9-dione, 6, were isolated from the underground organs of Ligularia platyglossa (Franch.) Hand.-Mazz. Their structures were elucidated by spectroscopic methods including single-crystal X-ray diffraction analysis (2 and 3). Their in vitro cytotoxicities against seven cancer cell lines (BGC-823, A549, HL-60, B16, SMMC-7721, BEL7402, Hela) were evaluated. Compounds 2, 3, 5 showed cytotoxic activities on HL-60 cancer cells with IC50 in the range of 24.0 to 51.1 microM, whereas compound 3 exhibited only weak cytotoxic activity against the B16, BEL7402 and Hela cancer cells. Flow cytometric analysis indicated that compound 3 induces Hela cells to apoptotic death after 48 h treatment with 0.38 mM of this compound.     

Antiproliferative and apoptotic sesquiterpene lactones from Carpesium faberi

Four new (1-4) and 13 known (5-17) sesquiterpene lactones along with two known diterpenes (18, 19) were isolated from the whole plant of Carpesium faberi. The new structures were elucidated by means of spectroscopic techniques and some chemical transformations to be pseudoguaian-1α(H)-8α,12-olide-4β-O-β-d-glucopyranoside (1), 4β,10α-dihydroxy-5α(H)-1,11(13)-guaidien-8α,12-olide (2), 4β,10β-dihydroxy-5α(H)-1, 11(13)-guaidien-8β,12-olide (3), and (4S)-acetyloxyl-11(13)-carabren-8β,12-olide (4). All isolates were tested against MCF-7 human breast cancer cells using the MTT assay. Among them, the sesquiterpene lactones (except tomentosin 17) possessing an α-methylene-γ-lactone moiety were found to have in vitro antiproliferative activities, with IC₅₀ values of 3.0-38.8 μg/mL. The effects of four selected sesquiterpene lactones (guaianolide 2, carabranolide 4, pseudoguaianolide 9, eudesmanolide 13) on the cell cycle were examined using flow cytometry (FCM).     

Sablacaurin A and B, two 19-nor-3,4-seco-lanostane-type triterpenoids from Sabal causiarum and Sabal blackburniana, respectively

In search for bioactive compounds from Sabal species, sablacaurin A [25-ethyl,23-methyl-19-nor-24-methylene-3,4-seco-4(28)-lanosten-10,3-olide] and sablacaurin B [24-ethyl,24-methyl-19-nor-3,4-seco-4(28),25(26)-lanostadiene-10,3-olide], the first 19-nor lanostane derivatives of the 3,4-seco type with a spiro element, have been isolated from the leaves of Sabal causiarum and Sabal blackburniana respectively, together with the known squalene (S. blackburniana) and ss-sitosterol (S. causiarum). From leaves of Sabal peregrina, the known triterpenes 3-oxo-24-methylenecycloartane and 24-methylcycloart-25(26)-en-3-one were isolated. The structures of these compounds were established from spectroscopic studies.     

Phytotoxins from the fungus Malbranchea aurantiaca

Bioassay-directed fractionation of an ethyl acetate extract from cultures of the fungus Malbranchea aurantiaca led to the isolation of two phytotoxic compounds, namely, 1-hydroxy-2-oxoeremophil-1(10),7(11),8(9)-trien-12(8)-olide (1) and penicillic acid (2). The structure of 1 was established by spectroscopic and X-ray crystallographic analyses. Metabolites 1 and 2 caused significant inhibition of radicle growth of Amaranthus hypochondriacus with IC(50) values 6.57 and 3.86 microM, respectively. In addition, 1 inhibited activation of the calmodulin-dependent enzyme cAMP phosphodiesterase (IC(50)=10.2 microM).     

Biotransformation of betulinic and betulonic acids by fungi

Betulinic acid (1), a triterpenoid found in many plant species, has attracted attention due to its important pharmacological properties, such as anti-cancer and anti-HIV activities. The closely related, betulonic acid (2) also has similar properties. In order to obtain derivatives potentially useful for detailed pharmacological studies, both compounds were submitted to incubations with selected microorganisms. In this work, both were individually metabolized by the fungi Arthrobotrys, Chaetophoma and Dematium, isolated from the bark of Platanus orientalis as well as with Colletotrichum, obtained from corn leaves; such fungal transformations are quite rare in the scientific literature. Biotransformations with Arthrobotrys converted betulonic acid (2) into 3-oxo-7beta-hydroxylup-20(29)-en-28-oic acid (3), 3-oxo-7beta,15alpha-dihydroxylup-20(29)-en-28-oic acid (4) and 3-oxo-7beta,30-dihydroxylup-20(29)-en-28-oic acid (5); Colletotrichum converted betulinic acid (1) into 3-oxo-15alpha-hydroxylup-20(29)-en-28-oic (6) acid whereas betulonic acid (2) was converted into the same product and 3-oxo-7beta,15alpha-dihydroxylup-20(29)-en-28-oic acid (4); Chaetophoma converted betulonic acid (2) into 3-oxo-25-hydroxylup-20(29)-en-28-oic acid (7) and both Chaetophoma and Dematium converted betulinic acid (1) into betulonic acid (2). Those fungi, therefore, are useful for mild, selective oxidations of lupane substrates at positions C-3, C-7, C-15, C-25 and C-30.     

Constituents of the stem bark of Discopodium penninervium and their LTB4 and COX-1 and -2 inhibitory activities

The stem bark of Discopodium penninervium afforded a withanolide, 6alpha,7alpha-epoxy-1-oxo-5alpha,12alpha,17alpha-trihydroxywitha-2,24-dienolide (1) and a coloratane sesquiterpene, 7alpha,11alpha-dihydroxy-4(13),8-coloratadien-12,11-olide (4) along with five known compounds, withanone (2), 5alpha,17beta-dihydroxy-6alpha,7alpha-epoxy-1-oxowitha-2,24-dienolide (3), 7alpha,11alpha-dihydroxy-8-drimen-12,11-olide (5), withasomnine (6), and (E,Z)-9-hydroxyoctadeca-10,12-dienoic acid (7). The identity of the compounds was established on the basis of spectroscopic data analysis. All compounds were assessed for inhibition of leukotriene metabolism in an in vitro bioassay using activated human neutrophile granulocytes, and for in vitro cycloxygenase-1 and -2 inhibition from sheep cotyledons and seminal vesicles, respectively. In the leukotriene biosynthesis assay all compounds tested at a concentration of 50 microM exhibited activity with percentage inhibitions ranging from 11.5 to 36.6. The withanolide, 1, displayed a 46.4% inhibition of COX-2 and a 22.9% inhibition of LTB(4) formation at 50 microM concentration. Compounds 4 and 6 inhibited LTB(4) biosynthesis but showed minor inhibition of COX-1 and COX-2. The remaining compounds, on the other hand, were found to be inactive on COX enzymes.     

Sesquiterpenes from Warburgia ugandensis and their antimycobacterial activity

The dichloromethane extract of the stem bark of Warburgia ugandensis afforded three new coloratane sesquiterpenes, namely: 6alpha,9alpha-dihydroxy-4(13),7-coloratadien-11,12-dial (1), 4(13),7-coloratadien-12,11-olide (2), and 7beta-hydroxy-4(13),8-coloratadien-11,12-olide (3), together with nine known sesquiterpenes, i.e., cinnamolide-3beta-acetate (4), muzigadial (5), muzigadiolide (6), 11alpha-hydroxymuzigadiolide (7), cinnamolide (8), 7alpha-hydroxy-8-drimen-11,12-olide (9), ugandensolide (10), mukaadial (11), ugandensidial (12), and linoleic acid (13). Their structures were assigned on the basis of 1D and 2D-NMR spectroscopic and GC-MS analysis. The compounds were examined for their antimycobacterial activity against Mycobacterium aurum, M. fortuitum, M. phlei and M. smegmatis; and the active constituents showed MIC values ranged from 4 to 128 microg/ml compared to the antibiotic drugs ethambutol (MIC ranged from 0.5 to 8 microg/ml) and isoniazid (MIC ranged from 1 to 4 microg/ml).     

Triterpenoid saponins from Schefflera arboricola

Nine triterpenoid saponins were isolated from the leaves and stems of Schefflera arboricola. The saponins were characterised, on the basis of chemical and spectral evidence, as 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucuronopyranosyl] oleanolic acid, 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucuronopyranosyl] echinocystic acid, 3-O-[beta-D-apiofuranosyl-(1-->4)-beta-D-glucuronopyranosyl] oleanolic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-ramnopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid, 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[beta-D-galactopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid, 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[beta-D-galactopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester, 3-O-beta-D-apiofuranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid and 3-O-beta-D-apiofuranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester.     

ent-Labdane glycosides from the aquatic plant Potamogeton lucens and analytical evaluation of the lipophilic extract constituents of various Potamogeton species

Two new ent-labdane glycosides, one known furano-ent-labdane and a new hydroxylated fatty acid were isolated from the dichloromethane extract of the freshwater aquatic plant Potamogeton lucens. The new compounds were assigned the structures of beta-d-glucopyranosyl-8(17),13-ent-labdadien-16,15-olid-18-oate, 18-beta-d-glucopyranosyloxy-8(17),13-ent-labdadien-16,15-olide and 13(R)-hydroxy-octadeca-(9Z,11E,15Z)-trien-oic acid by spectroscopic means. The algicidal activity of these compounds was tested against Raphidocelis subcapitata. Based on our previous study of Potamogeton pectinatus, other constituents were identified in P. lucens by LC-UV-MS, LC-NMR and GC-MS. The lipophilic extract profiles of both species are presented. Two other species, Potamogeton perfoliatus and P. crispus, were also investigated by analytical comparison of their non-polar extracts. The distribution of ent-labdanes characterized in Potamogeton is summarized.     

Terpenoids from Microliabum polymnioides

The phytochemical study of M. polymnioides led to the isolation of two sesquiterpene lactones namely: 11alphaH-dihydrozaluzanin E and 1beta-hydroxy-4-oxo-11betaH-4-noreudesman-6,12-olide. Their structures were determined by spectroscopic methods. The relative stereochemistry was established by a combination of coupling constant analysis, NOESY correlations and molecular modeling. Three related known sesquiterpene lactones were also identified, and these data were used for chemotaxonomical purposes.