Minor cytotoxic and antibacterial compounds from the rhizomes of Amomum aculeatum.

A new cytotoxic 1,7-dioxa-dispiro[5.1.5.2]pentadeca-9,12-dien-11-one derivative, aculeatin D, and a new alkenone, 5-hydroxy-hexacos-1-en-3-one, have been isolated as minor compounds from the rhizomes of Amomum aculeatum. Their structures have been determined mainly by NMR spectroscopy and mass spectrometry. Aculeatin D showed high cytotoxicity against the KB and the L-6 cell line with IC(50) of 0.38 microg/ml and 1 microg/ml, respectively. Additionally, it revealed remarkable activity against two Plasmodium falciparum strains, as well as against Trypanosoma brucei rhodesiense and Trypanosoma cruzi. 5-Hydroxy-hexacos-1-en-3-one exhibited neither cytotoxic nor antiprotozoal activity, whereas antibacterial testing against Bacillus cereus, Escherichia coli and Staphylococcus epidermidis showed moderate to strong activity for both compounds.

New tirucallane-type triterpenes from Dysoxylum variabile.

Eight new tirucallane-type triterpenes, dyvariabilins A-H (1-8), three known tirucallanes, niloticin (9), dihydroniloticin (10), and tirucalla-7,24-diene-3 beta,23-diol (11), and two known sesquiterpenes, 1-(1-hydroxy-2-methylpropyl)-3a-methyl-7-methyleneoctahydroinden-4-ol and (+)-aphanamol I, were isolated from the stem bark of Dysoxylum variabile. Tirucallanes 1 and 11 with an allylic hydroxy group in the side chain and dyvariabilin C (3) with an alpha-epoxy group at positions 7 and 8 showed high instability in acidic medium and formed five hitherto unknown semisynthetic tirucallanes. Dyvariabilins B (2) and C (3) as well as the mixtures of dyvariabilins E and F (5 and 6) and dyvariabilins G and H (7 and 8) showed weak cytotoxicity against KB cells.

New prenylated bi- and tricyclic phloroglucinol derivatives from Hypericum papuanum.

Five new prenylated tricyclic and three new bicyclic acylphloroglucinol derivatives have been isolated by bioactivity-guided fractionation of the petroleum ether extract of the dried aerial parts of Hypericum papuanum. The tricyclic compounds (1--5) were named papuaforins A--E. The bicyclic compounds were isolated together with their corresponding tautomers and were named hyperguinones A and B (6/6a,7/7a) and hyperpapuanone (8/8a), respectively. Their structures were elucidated on the basis of extensive 1D and 2D NMR experiments, as well as mass spectrometry. Furthermore, the cytotoxicity toward KB nasopharyngeal carcinoma cells and the antibacterial activity of the isolated compounds were determined.

New phloroglucinol derivatives from Hypericum papuanum.

Bioactivity-guided fractionation of the petroleum ether extract of the aerial parts of Hypericum papuanum led to the isolation of five new tricyclic phloroglucinol derivatives. On the basis of extensive 1D and 2D NMR experiments as well as MS studies, their structures were elucidated as the C-3 epimers of 8-hydroxy-4,4, 7-trimethyl-9-(2-methylpropionyl)-3-(1-methylvinyl)-5beta -H-tricyclo[ 5.3.1.0(1,5)]undec-8-ene-10,11-dione (1,2); the C-3 epimers of 8-hydroxy-4,4, 7-trimethyl-9-(2-methylbutyryl)-3-(1-methylvinyl)-5beta-H-++ +tricyclo[5. 3.1.0(1,5)]undec-8-ene-10,11-dione (3, 4), and 8-hydroxy-4,4, 7-trimethyl-9-(2-methylpropionyl)-5beta-H-tricyclo[5.3 .1.0(1, 5)]undec-8-ene-10,11-dione (5), and their corresponding tautomers (1a, 2a, 3a, 4a, 5a). Compounds 1/1a-5/5a were named ialibinones A-E, respectively. Compounds 1/1a-4/4a showed antibacterial activity against Bacillus cereus, Staphylococcus epidermidis, and Micrococcus luteus.

Bioactive coumarin derivatives from the fern Cyclosorus interruptus.

Three new coumarin derivatives, compounds 1-3, three new furanocoumarins, compounds 4-6, and a novel dioxocane derivative, compound 7, were isolated from the fern Cyclosorus interruptus (Willd.) H. Itô. Based on spectrometric and spectroscopic analysis (FAB or El mass spectrometry as well as 1D and 2D NMR experiments) their structures were characterised as 5,7-dihydroxy-6-methyl-4-phenyl-8-(3-phenylpropionyl)-1-benzopyran-2-one (1), 5,7-dihydroxy-6-methyl-4-phenyl-8-(3-phenyl-trans-acryloyl)-1- benzopyran-2-one (2), 5,7-dihydroxy-8-(2-hydroxy-3-phenylpropionyl)-6-methyl-4-phenyl-1- benzopyran-2-one (3), 8-benzyl-5,8-dihydroxy-6-methyl-4-phenylfuro[2,3-h]-1-benzopyran-2,9- dione (4), 8-benzyl-5,8 beta,9 beta-trihydroxy-6-methyl-4-phenyl-8,9-dihydro- furo[2,3-h]-1-benzopyran-2-one (5), 8-benzyl-5,8 beta,9 alpha-trihydroxy-6-methyl-4-phenyl-8,9-dihydro- furo[2,3-h]-1-benzopyran-2-one (6) and 5,11-dihydroxy-6-methyl-4-phenyl-11-(1-phenylmethyl)-7,10-dioxocane [5,6-h]-1-benzopyran-2,12-dione (7). For these compounds we propose the trivial names interruptins A-F. Compounds 1, 5/6 and 7 showed antibacterial activity while compounds 1 and 2 were cytotoxic to a KB cell line.

Acylated flavonol glycosides from leaves of Stenochlaena palustris.

From the leaves of Stenochlaena palustris five new O-acylated flavonol glycosides, stenopalustrosides A-E (1-5), have been isolated along with five known compounds, kaempferol 3-O-(3' '-O-E-p-coumaroyl)-(6' '-O-E-feruloyl)-beta-D-glucopyranoside (6), kaempferol 3-O-(3' ',6' '-di-O-E-p-coumaroyl)-beta-D-glucopyranoside (7), kaempferol 3-O-(3' '-O-E-p-coumaroyl)-beta-D-glucopyranoside (8), kaempferol 3-O-(6' '-O-E-p-coumaroyl)-beta-D-glucopyranoside (9); and kaempferol 3-O-beta-D-glucopyranoside (10). The structures of the isolates were elucidated by spectroscopic methods, mainly 1D and 2D NMR. Compounds 1-4 showed significant antibacterial activities against Gram-positive strains. The structural difference between the isolated antibacterial and nonantibacterial compounds is discussed.

Gibbilimbols A-D, cytotoxic and antibacterial alkenylphenols from Piper gibbilimbum.

Fractionation of the petroleum ether extract from the leaves of Piper gibbilimbum collected in Papua New Guinea afforded four new alkenylphenols, gibbilimbols A-D (1-4). The structures of the isolates were elucidated by spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy. Gibbilimbols A-D were found to be toxic to brine shrimp with an LC50 of approximately 5 microg/mL. Gibbilimbols A-D were further found to be cytotoxic toward KB nasopharyngal carcinoma cells (ED50 7.8-2.1 microg/mL). All isolates also showed antibacterial activity toward Staphylococcus epidermidis and Bacillus cereus.

Dammarane Triterpenes from the Leaves of Securinega melanthesoides

Two new dammarane triterpenoids, trans-securinegin [(20S)-24-methylidenedammarane-3alpha-yl(2E)-3-(4-hydroxyphenyl)-2-propenate (1)] and cis-securinegin [(20S)-24-methylidenedammarane-3alpha-yl(2Z)-3-(4-hydroxyphenyl)-2-propenate (2)], were isolated from the leaves of Securinega melanthesoides, along with the known compound bergenin. The structures of 1 and 2 were elucidated using spectroscopic methods, mainly 2D NMR techniques.

Antibacterial triterpenoids from Dillenia papuana and their structure-activity relationships.

Two new oleanene-type triterpenoids, dillenic acids D and E, have been isolated from the leaves and stems of Dillenia papuana together with the new natural product 3-oxoolean-12-en-30-oic acid. Together with these compounds, the known compound, betulinic acid (3 beta-hydroxy-20(29)-lupen-28-oic acid) was isolated as the major component of the fractions studied. Dillenic acids D and E were characterized as 2,3-seco-2-oxoolean-12-en-3-methylester-30-oic acid and 1 alpha,3 beta-dihydroxyolean-12-en-30-oic acid and their nuclear magnetic resonance data were unambiguously assigned using two-dimensional nuclear magnetic resonance techniques. A comparison of antibacterial activities of these compounds with the earlier reported dillenic acids A-C indicated that, aside from a double bond in gamma- or delta-position to a carboxylic group, a ketone function in ring A of an oleanene-skeleton may be required for the observed activity.

Biological screening of traditional medicinal plants from Papua New Guinea.

Based on ethnopharmacological literature, 17 species of medicinal plants used in the traditional medicine in Papua New Guinea were collected. Extracts of different polarities were tested in a preliminary biological screening for their antimicrobial (Escherichia coli, Bacillus subtilis, Micrococcus luteus and Penicillium oxalicum) and molluscicidal activity against Biomphalaria glabrata as well as for their toxicity to brine shrimp. The pretreated plant extracts were also investigated for their ability to inhibit protein kinase C and tyrosine-specific protein kinase of epidermal growth factor receptor. Furthermore, all plants were screened for the presence of alkaloids.

Antibacterial triterpenoid acids from Dillenia papuana.

Three new oleanene-type triterpenoids, dillenic acids A [1], B [2], and C [3], and two known compounds, 3-oxoolean-1,12-dien-30-oic acid [4] (a new natural product) and the lupene derivative betulinaldehyde, have been isolated from the Papua New Guinean medicinal plant Dillenia papuana. The structures of the new compounds were elucidated as 2 alpha-hydroxy-3-oxoolean-12-en-30-oic acid, 2-oxo-3 beta-hydroxyolean-12-en-30-oic acid and 1 alpha-hydroxy-3-oxoolean-12-en-30-oic acid. The 1H- and 13C-nmr data of all new compounds were assigned unambiguously using a variety of 2D nmr experiments including 1H-1H-COSY, HMQC, HMBC, and NOESY experiments. Of these compounds, 1-4 showed antibacterial activities against Bacillus subtilis, Escherichia coli, and Micrococcus luteus.

Cytotoxic and antibacterial dihydrochalcones from Piper aduncum.

Bioactivity-guided fractionation of a CH2Cl2 extract from the leaves of Piper aduncum afforded three new dihydrochalcones, piperaduncins A [3], B [4], and C [5], as well as two known dihydrochalcones, 2',6'-dihydroxy-4'-methoxydihydrochalcone [1] and 2',6',4-trihydroxy-4'-methoxydihydrochalcone [2] (asebogenin), together with sakuranetin, anodendroic acid methyl ester, and the carotenoid lutein. The structures of the isolates were elucidated by spectroscopic methods, mainly 1D- and 2D nmr spectroscopy. The proposed stereochemistry for compound 4 was deduced by NOESY spectroscopy and the corresponding energy minimum was established by molecular modelling calculations and translated into a 3D structure.

Five new prenylated p-hydroxybenzoic acid derivatives with antimicrobial and molluscicidal activity from Piper aduncum leaves.

Five new prenylated benzoic acid derivatives, methyl 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxybenzoate (1), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-hydroxybenzoate (2), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (3), methyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (4), and 4-hydroxy-3-(3-methyl-2-butenyl)-5-(3-methyl-2-butenyl)-benzoic acid (5) were isolated from the dried leaves of Piper aduncum L. (Piperaceae). Together with the new metabolites, four known prenylated benzoic acid derivatives, 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (6), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (nervogenic acid, 7), methyl 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoate (8), and methyl 4-hydroxy-3-(3-methyl-2-butenyl)-benzoate (9) as well as, dillapiol (10), myristicin, and the three sesquiterpenes humulene, caryophyllene epoxide, and humulene epoxide were isolated. Compounds 7, 8, and 9 are reported as natural products for the first time. The structures of the isolates were elucidated by spectroscopic methods, mainly 1D-and 2D-NMR spectroscopy. Isolates 4-7, 9, and 10 were molluscicidal while 2, 5-7, and 9 displayed significant antibacterial activities.

New phenolic glucosides from the leaves of Eurya tigang.

Three new compounds, 6'-O-coumaroyl-1'-O-[2-(4-hydroxyphenyl)ethyl]-beta-D-glucopyra nos ide [1] (eutigoside A), 6'-O-coumaroyl-1'-O-[2-(1-hydroxy-4-oxo-2,5-cyclohexadien-1- yl)ethyl]-beta-D-glucopyranoside [2] (eutigoside B), and 6'-O-cinnamoyl-1'-O-[2-(1-hydroxy-4-oxo-2,5-cyclohexadien-1-yl)eth yl]- beta-D-glucopyranoside [3] (eutigoside C) have been isolated from the leaves of Eurya tigang, along with other known compounds (afzelin, quercitrin, p-coumaric acid, methyl-alpha-D-fructofuranoside, isorengyol, and euryanoside). Their structures were determined by chemical and spectroscopic methods (uv, ir, ms, 1H-1H COSY, and 1H-13C COSY).

Indole alkaloids with in vitro antiproliferative activity from the ammoniacal extract of Nauclea orientalis.

Nine angustine-type alkaloids were isolated from ammoniacal extracts of Nauclea orientalis L. (Rubiaceae). Three of them, 10-hydroxyangustine and the two diastereoisomeric 3,14-dihydroangustolines, have not been described in the literature thus far. The structures of the isolates were determined with spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy. The compounds were found to exhibit in vitro anti-proliferative activity against the human bladder carcinoma T-24 cell line and against EGF (epidermal growth factor)-dependent mouse epidermal keratinocytes. By using overpressure layer chromatography, it was shown that minor quantities of these alkaloids occur in dried Nauclea orientalis leaves. The use of ammonia in the extraction process results in a significant increase in the formation of angustine-type alkaloids from strictosamide-type precursors.

New indole alkaloid glycosides from Nauclea orientalis.

Two new indole alkaloid glycosides, 10-hydroxystrictosamide and 6'-O-acetylstrictosamide, as well as the known alkaloids strictosamide and vincosamide were isolated from the leaves of Nauclea orientalis L. The structures of the isolated compounds were determined using spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy.