Cytotoxic germacranolides and acyclic diterpenoides from the seeds of Carpesium triste

Four new highly oxygenated germacranolides (1, 4, 6, and 7) and four new acyclic diterpenes (8-11), along with three known germacranolides (2, 3, and 5), were isolated from the seeds of Carpesium triste. The structures of the new compounds were elucidated by spectroscopic methods including IR, HRESIMS, and 1D and 2D NMR experiments, and the absolute configurations of compounds 1 and 8-10 were established by CD and Mosher's methods, respectively. Compounds 1, 2, and 4-10 were evaluated for their in vitro cytotoxic activity against cultured SMMC-7721 (human hepatoma), HL-60 (human promyelocytic leukemia), and L02 (human hepatocyte) cell lines. Compounds 1, 2, and 4-7 exhibited significant cytotoxicity against HL-60 cells, and compound 10 exhibited cytotoxicity against SMMC-7721 cells.     

Antimicrobial metabolites from the Paracel Islands sponge Agelas mauritiana

Four new alkaloids, (-)-8'-oxo-agelasine D (2), ageloxime B (3), (+)-2-oxo-agelasidine C (4), and 4-bromo-N-(butoxymethyl)-1H-pyrrole-2-carboxamide (5), and the known compound (-)-ageloxime D (1) were isolated from the marine sponge Agelas mauritiana. Their chemical structures were established on the basis of spectroscopic analysis. Compounds 1 and 3 both showed antifungal activity against Cryptococcus neoformans and antileishmanial activity against Leishmania donovani in vitro. Compound 3 also exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureusin vitro.     

Antiplasmodial triterpenoids from Ekebergia capensis

From the stem bark of Ekebergia capensis, 10 new triterpenoid compounds, ekeberins A (1), B (2), C1 (3), C2 (4), C3 (5), D1 (6), D2 (7), D3 (8), D4 (9), and D5 (10), were isolated together with 17 known compounds. The structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the Mosher ester method. Several of these compounds were screened in vitro against both chloroquine (CQ)-sensitive and -resistant Plasmodium falciparum isolates and were found to exhibit moderate antiplasmodial activity, with compounds 20 (7-deacetoxy-7-oxogedunin) and 27 (2-hydroxymethyl-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene) showing IC50 values of 6 and 7 microM, respectively. Compound 27 at a dose of 500 mg/kg showed moderate parasitemia suppression of 52.9% against P. berghei NK 65 in a mouse model.     

Caffeic acid esters and lignans from Piper sanguineispicum

Three new caffeic acid esters (1-3), four new lignans (4-7), and the known compounds (7'S)-parabenzlactone (8), dihydrocubebin (9), and justiflorinol (10) have been isolated from leaves of Piper sanguineispicum. Their structures were determined by spectroscopic methods, including 1D and 2D NMR, HRCIMS, CD experiments, and chemical methods. Compounds 1-10 were assessed for their antileishmanial potential against axenic amastigote forms of Leishmania amazonensis. Caffeic acid esters 1 and 3 exhibited the best antileishmanial activity (IC(50) 2.0 and 1.8 μM, respectively) with moderate cytotoxicity on murine macrophages.     

Nematicidal epipolysulfanyldioxopiperazines from Gliocladium roseum

Five new verticillin-type epipolysulfanyldioxopiperazines, gliocladine A (1), B (2), C (3), D (4), and E (5), were isolated from wheat solid-substrate fermentation of Gliocladium roseum 1A, along with four known compounds, verticillin A (6), 11'-deoxyverticillin A (7), Sch52900 (8), and Sch52901 (9). Their structures were elucidated by extensive 1D and 2D NMR studies, MS, and chemical transformations. In vitro immersion tests showed that all nine compounds exhibited antinematodal activity against Caenorhabditis elegans and Panagrellus redivivus. The monomeric epipolysulfanydioxopiperazines (3-5), with the indole moiety, were found to be less active than the dimeric compounds (1, 2, 6-8).     

New bromotyrosine derivatives from an association of two sponges, Jaspis wondoensis and Poecillastra wondoensis

Three new bromotyrosine derivatives (4-6) were isolated from an association of two sponges, Jaspis wondoensis and Poecillastra wondoensis, along with the previously described (E,E)-psammaplin A (1), (E,Z)-psammaplin A (2), psammaplin D (3), bisaprasin (7), and (3-bromo-4-hydroxyphenyl)acetonitrile (8). The structures of the new compounds were established on the basis of NMR and MS spectroscopic analysis. The compounds 1, 3, and 5-7 displayed significant cytotoxicity against human lung (A549), ovarian (SK-OV-3), skin (SK-MEL-2), CNS (XF498), and colon (HCT15) cancer cell lines. Compounds 3-7 were further evaluated for antibacterial activity against methicillin- or ofloxacin-resistant Staphylococcus strains. Compound 4 exhibited more potent antibacterial activity than meropenem against several strains.     

Ymf 1029A-E, preussomerin analogues from the fresh-water-derived fungus YMF 1.01029

Five new preussomerin analogues, ymf 1029A (1), B (2), C (3), D (4), and E (5), were isolated from the liquid cultures of an unidentified freshwater fungus YMF 1.01029, along with four known compounds, preussomerin C (6), preussomerin D (7), (4RS)-4,8-dihydroxy-3,4-dihydronaphthalen-1(2H)-one (8), and 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one (9). The structures of new metabolites were determined by analysis of NMR and MS data and by analogy with the data for the known bis-spirobisnaphthalene preussomerins. In vitro immersion experiments showed that these metabolites displayed weak nematicidal activity against Bursaphelenchus xylophilus, while compound 7 was the most potent. This is the first report of these compounds, which antagonize the Bursaphelenchus xylophilus nematode.     

Phenolic constituents from Dalbergia cochinchinensis

Three new phenolic compounds (1-3), along with five known phenolics, 4'-hydroxy-2'-methoxychalcone (4), latinone (5), dalbergiphenol (6), 7-hydroxyflavanone, and dalbergin (7), have been isolated from the stems of Dalbergia cochinchinensis. The structures of 1-3 were established by spectroscopic techniques including 1D and 2D NMR methods. The inhibitory activity against testosterone 5 alpha-reductase, which causes androgen-dependent diseases, was also examined for selected compounds.     

Antimicrobial triterpenoids from Vladimiria muliensis

A new triterpenoid with a rearranged ursane skeleton, 3beta-acetoxyl-11alpha-methoxybauer-8-en-7alpha-ol ( 1), two new ursane triterpenoids, 1alpha,5alpha-dioxy-11alpha-hydroxyurs-12-en-3-one ( 2) and urs-3beta,13alpha,18beta-triol ( 3), together with three known ursane triterpenoids ( 4- 6) were isolated from the rhizome of Vladimiria muliensis. Their structures were elucidated on the basis of spectroscopic methods (IR, EIMS, HRESIMS, 1D and 2D NMR, and X-ray crystallography diffraction). Compounds 2 and 4 exhibited modest antimicrobial activity against Escherichia coli, Candida albicans, Pseudomonas aeruginosa, Enterococcus faecalis, Bacillus cereus, and Staphylococcus aureus.     

Cytotoxic withanolides from Tubocapsicum anomalum

Fifteen new withanolides (1-8, 11-17) and two known withanolides, withanolide D (9) and 17alpha-hydroxywithanolide D (10), were isolated from the stems, roots, and leaves of Tubocapsicum anomalum using bioassay-directed fractionation. The structures were determined by spectroscopic and chemical methods, and the absolute configurations were established by CD analysis and by the Mosher ester method. The structure of 1 and 3 were further confirmed by X-ray crystallographic analysis. Compounds 1, 4-6, 8-10, and 13 showed significant cytotoxic activity against Hep G2, Hep 3B, A-549, MDA-MB-231, MCF-7, and MRC-5 cell lines.     

Iridoid glucosides and p-coumaroyl iridoids from Viburnum luzonicum and their cytotoxicity

Four new iridoids glucosides (1-4) and seven new iridoid aglycons (5-11) bearing (E)- or (Z)-p-coumaroyl groups were isolated from a methanol extract of the dried leaves of Viburnum luzonicum collected in Kaoshiung, Taiwan. The structures of the new compounds, named luzonoside A (1), luzonoside B (2), luzonoside C (3), luzonoside D (4), luzonoid A (5), luzonoid B (6), luzonoid C (7), luzonoid D (8), luzonoid E (9), luzonoid F (10), and luzonoid G (11), were elucidated by analysis of spectroscopic data and comparison with values for previously known analogues. Among the iridoids isolated in the present study, glucosides 1 and 2, and their aglycons 5-9, exhibited moderate inhibitory activity against HeLa S3 cancer cells, whereas 3 and 4 showed no cytotoxicity even at 100 microM.     

New cytotoxic indole alkaloids from Tabernaemontana calcarea from the Madagascar rainforest

Bioassay-directed fractionation of the alkaloid portion of a CH(2)Cl(2)-MeOH extract of Tabernaemontana calcarea resulted in the isolation of the three new cytotoxic indole alkaloids, 1-3, and the 12 known alkaloids voacangine (4), isovoacangine (5), coronaridine (6), 11-hydroxycoronaridine (7), voacristine (8), 19-epi-voacristine (9), isovoacristine (10), ibogamine (11), 10-methoxyibogamine (12), 11-methoxyibogamine (13), heyneanine (14), and 19-epi-heyneanine (15). The structures of the new compounds 1-3 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic interpretation. All the compounds exhibited cytotoxic activity against the A2780 ovarian cancer cell line.     

Indole glucoalkaloids from Chimarrhis turbinata and their evaluation as antioxidant agents and acetylcholinesterase inhibitors

As part of our study on bioactive agents from Brazilian rainforest plants, two new glucoalkaloids, 3,4-dehydro-strictosidine (1) and 3,4-dehydro-strictosidinic acid (2), were isolated from Chimarrhis turbinata, along with seven known glucoalkaloids, cordifoline (3), strictosidinic acid (4), strictosidine (5), 5 alpha-carboxystrictosidine (6), turbinatine (7), desoxycordifoline (8), and harman-3-carboxylic acid (9). The structures of the new alkaloids were established on the basis of comprehensive spectral analysis, mainly 1D and 2D NMR experiments, as well as high-resolution HRESIMS. Alkaloid 3 showed strong free-radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as pronounced antioxidant activity evidenced by redox properties measured by ElCD-HPLC. Additionally, alkaloids 1-9 were submitted to TLC screening for acetylcholinesterase inhibitors. Both 7 and 8 were shown to be moderate acetylcholinesterase inhibitors at a concentration of 0.1 and 1.0 microM, respectively. In an in vitro rat brain assay, 7 showed moderate activity (IC(50) 1.86 microM), compared to the standard compound, galanthamine (IC(50) 0.92 microM).     

Activity of triterpenoid glycosides from the root bark of Mussaenda macrophylla against two oral pathogens.

Four new triterpenoid glycosides were isolated from the root bark of Mussaenda macrophylla. Their structures were determined as 3-O-beta-D-glucopyranosyl-28-O-alpha-L-rhamnopyranosyl-16alpha- hydrox y-23-deoxyprotobassic acid (1), 28-O-beta-D-glucopyranosyl-16alpha-hydroxy-23-deoxyprotobassic+ ++ acid (2), 3-O-beta-D-glucopyranosyl-28-O-alpha-L-rhamnopyranosyl-16alpha- hydrox yprotobassic acid (3), and 3-O-?[beta-D-glucopyranosyl-(1-->6)]-O-alpha-L-rhamnopyranosyl-(1-->2 )-O-beta-D-glucopyranosyl-(1-->2)?-O-beta-D-glucopyranosyl-(1-->3)-O- beta-D-glucopyranosyl-cycloarta-22,24-dien-27-oic acid (mussaendoside W, 4). Four known triterpenoids [3-O-acetyloleanolic acid (5), 3-O-acetyldaturadiol (6), rotundic acid (7), and 16alpha-hydroxyprotobassic acid (8)] were also isolated. The structures of 1-4 were determined by several spectroscopic techniques including 2D NMR methods. Compounds 1-6 showed inhibitory activity against a periodontopathic bacterium, Porphyromonas gingivalis, but were inactive against the cariogenic organism, Streptococcus mutans.     

Triterpenes from Garcia parviflora. Cytotoxic evaluation of natural and semisynthetic friedelanes

Three new friedelane-type triterpenes, 1,2-dehydro-2,3-secofriedelan-3-oic acid (1), 1β-hydroxyfriedelin (2), and 3β-hydroxyfriedelan-23-oic acid (3), and the known compounds friedelin-3,4-lactone (4), acetyl aleuritolic acid (5), 4-hydroxy-5-propionyl-1,3-di-O-methylpyrogallol, elemicin, and (-)-syringaresinol were isolated from the leaves of Garcia parviflora. The structures of 1-3 were elucidated by spectroscopic methods, including 1D and 2D NMR, HREIMS, X-ray, and CD analysis. Some derivatives of 2 (6-14) were prepared via oxidation, reduction, and esterification. The natural triterpenes and the semisynthetic friedelane derivatives were tested for cytotoxic activity against human cancer cell lines U251, PC-3, K562, HCT-15, MCF-7, and SKLU-1. Compound 5 was cytotoxic against U251 cells.     

Structure and cytotoxicity of diterpenoids from Isodon eriocalyx

A new ent-atisanoid, eriocatisin A (1), six new ent-abietanoids, eriocasins B-E (2-4, 7), 3-acetyleriocasin C (5), and 3β-acetoxyeriocasin D (6), and seven new ent-kauranoids, maoesins A-F (8, 10-14) and 3α-acetoxy-maoesin A (9), together with 21 known compounds, were isolated from the aerial parts of Isodon eriocalyx. The structures of 1-14 were determined by spectroscopic data interpretation. All compounds isolated were evaluated for their in vitro growth inhibitory activity against the HT-29, BEL-7402, and SK-OV-3 human cancer cell lines. Compounds 17, 18, and 20 showed inhibitory effects for all three tumor cell lines used, with IC(50) values in the range 2.1-7.3 μM.     

Antimalarial β-carboline and indolactam alkaloids from Marinactinospora thermotolerans, a deep sea isolate

Four new β-carboline alkaloids, designated marinacarbolines A-D (1-4), two new indolactam alkaloids, 13-N-demethyl-methylpendolmycin (5) and methylpendolmycin-14-O-α-glucoside (6), and the three known compounds 1-acetyl-β-carboline (7), methylpendolmycin (8), and pendolmycin (9) were obtained from the fermentation broth of Marinactinospora thermotolerans SCSIO 00652, a new actinomycete belonging to the family Nocardiopsaceae. Their structures were elucidated by extensive MS and 1D and 2D NMR spectroscopic data analyses. The structure of compound 1 was further confirmed by single-crystal X-ray crystallography. The new compounds 1-6 were inactive against a panel of eight tumor cell lines (IC50>50 μM) but exhibited antiplasmodial activities against Plasmodium falciparum lines 3D7 and Dd2, with IC50 values ranging from 1.92 to 36.03 μM.     

Cytotoxic diacetylenic spiroketal enol ethers from Plagius flosculosus

Three new diacetylenic spiroketal enol ethers named flosculins A (1), B (2), and C (3), along with five known compounds (4-8) of the same structural class, were isolated from the leaves of Plagius flosculosus. The structures were deduced by extensive 1D and 2D NMR spectroscopy and mass spectrometry. All isolated compounds exhibited significant cytotoxic activity against leukemia cells (Jurkat T and HL-60). Compounds 5-8 induced apoptosis in HL-60 cells with corresponding IC(50) values ranging from 4 to 6 microM.     

N-Methyl-4-hydroxy-2-pyridinone analogues from Fusarium oxysporum

Three new N-methyl-4-hydroxy-2-pyridinone analogues, 6-epi-oxysporidinone (3), the dimethyl ketal of oxysporidinone (4), and N-demethylsambutoxin (5), along with the known compounds (-)-oxysporidinone (1), (-)-sambutoxin (2), wortmannin (6), enniatin A (7), enniatin A1 (8), and enniatin B1 (9) were isolated from Fusarium oxysporum (N17B) by bioassay-guided fractionation. Compounds 1 and 3 showed selective fungistatic activity against Aspergillus fumigatus, and wortmannin had selective potent activity against Candida albicans. Moderate activity was observed with the enniatins 7-9 against C. albicans, Cryptococcus neoformans, and Mycobacterium intracellulare. Compounds 1-5 had no activity against the agriculturally important fungi Fusarium verticillioides (syn. F. moniliforme) and Aspergillus flavus.     

Cytotoxic triterpenoid saponins acylated with monoterpenic acid from Pithecellobium lucidum

Three new oleanane-type triterpene saponins, named pithelucosides A-C (1-3), together with two known saponins (4, 5) were isolated from the roots of Pithecellobium lucidum. The structures of the new saponins were established on the basis of extensive 1D and 2D NMR experiments and mass spectrometry and confirmed by acid and alkaline hydrolysis. Compounds 1-5 and 7 (pro-sapogenin obtained from the mild alkaline hydrolysate of 1) were evaluated for cytotoxic activity on five human tumoral cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780) and for hemolytic property against rabbit erythrocytes. Compounds 2-5 showed significant cytotoxic activities with IC50 values of 0.61-7.56 microM. All tested compounds did not exhibit any hemolytic activity in the concentration range 0.01-100 microM.