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From the crude ethanol extract of Wedelia trilobata leaves, hexane and dichloromethane fractions exhibited in vitro antimalarial activity against the Plasmodium falciparum parasite (strain PFB), with IC50 values of 27.0 and 13.0 μg/mL, respectively. Specifically, two new (9R)-eudesman-9,12-olide δ-lactones, wedelolide G (1) and wedelolide H (2), were isolated from the dichloromethane extract and showed IC50 values of 3.42 and 5.96 μM, respectively. Six known compounds are also present in the extract. The structures of 1⿿8 were elucidated through spectroscopic studies.

Decoction of Strychnopsis thouarsii is used in the Malagasy traditional medicine to combat malaria. We have shown that this traditional remedy prevents malaria infection by targeting Plasmodium at its early liver stage. Bioassay-guided fractionation of S. thouarsii stem barks extracts, using a rodent Plasmodium yoelii liver stage parasites inhibition assay, led to isolate the new morphinan alkaloid tazopsine (1) together with sinococuline (2) and two other new related morphinan analogs, 10-epi-tazopsine (3) and 10-epi-tazoside (4). Structures were characterized by 2D NMR, MS, and CD spectral analysis. Compounds 1-3 were found to fully inhibit the rodent P. yoelii liver stage parasites in vitro.

International audience; Myrobotinol (1) was isolated from the leaves of Myrioneuron nutans (Rubiaceae) and its structure determined from spectral data, including mass spectrometry and 2D NMR. This compound presents a new hexacyclic alkaloid skeleton including a 1,3-oxazine and aminal functionality. The absolute configuration of myrobotinol was established by using Mosher's method. A plausible biosynthetic pathway starting from L-lysine via Delta-piperideine was proposed for this hexacyclic alkaloid.

A new alkaloid, myrioneurinol ( 1 ), was isolated from the leaves of Myrioneuron nutans and its structure determined from spectral analysis, including mass spectrometry and 2D NMR. Myrioneurinol ( 1 ) presented an unprecedented fused tetracyclic skeleton. The absolute configuration was established by the modified Mosher's method, using ( R )- and ( S )-9-anthrylmethoxyacetic acid (9-AMAA). A plausible biosynthetic pathway starting from l -lysine via Δ-piperideine was proposed for 1 in comparison with nitraramine biosynthesis and related alkaloids.

Two new sesquiterpene lactones, wedelolides A (1) and B (2), were isolated by bioassay-guided fractionation from the leaves of Wedelia trilobata, together with known trilobolides 6-O-isobutyrate (3) and 6-O-methacrylate (4). The compounds 1 and 2 were the first examples of an unprecedented framework: a novel sesquiterpene delta-lactone, (9R)-eudesman-9,12-olide. The structures of the antimalarial wedelolides A (1) and B (2) were determined on the basis of MS and 2D NMR spectral analysis. The absolute configuration of eight carbon stereocenters of compounds 1 and 2 was determined to be 1S,4S,5S,6R,7S,8S,9R,10S by mean of auxiliary chiral MTPA derivatives.

Three new compounds, prepromalabaricone B (1) and two dimeric acylphenols, giganteones A (2) and B (3) were isolated from EtOAc extract of the fruits of Myristica gigantea (Myristicaceae), together with known promalabaricone C (4), malabaricones A-C (5-7) and maingayone (8). The structures were determined by mass and 2D NMR spectral analysis, and the enzymatic synthesis of giganteones A and B was performed from malabaricone C. Both 2 and 3 possess significant cytotoxic activity in vitro against human nasopharynx KB cells. The structure determination of 1, alkylphenol precursor of malabaricone, and of 2 and 3, acyphenol dimers is described. An enzymatic synthesis of 2 and 3 from malabaricone C was performed.

The purpose of the present work has been to seek a correlation of potential predictive value, demonstrating redox control of cytotoxicity toward human nasopharynx carcinoma (KB) cells by seven 5-hydroxy-7-methoxyflavones, together with two glycoside derivatives, all extracted from Lethedon tannaensis. In this approach, redox control is characterized by a physicochemical parameter expressing quantitatively the relative electron-donating power of the flavones, this parameter being the second order rate constant, kdelta, for quenching of singlet oxygen O2 (1deltag). This rate constant kdelta is usually related to the ability of a given molecule D to donate an electron and, thus, with the reduction potential E of the couple (D*+/D). Our results show that the flavone toxicity is linearly correlated with ease of oxidation: the higher the rate constant of reaction with singlet oxygen, the easier the oxidation, the less positive or more negative the reduction potential ((D*+/D), the higher the cytotoxicity. The results suggest new screening strategies to identify and improve potential antitumor drugs.

Harringtonolide (= hainanolide) is a complex polycyclic fused norditerpene isolated from CEPHALOTAXUS HARRINGTONIA var. DRUPACEA. In spite of its appealing biological properties - we measured an IC (50) of 43 nM on KB cells and a significant antifungal activity - its absolute configuration has not yet been firmly established. This was done herein using X-ray anomalous scattering after bromination of the tropone ring, unambiguously giving the stereochemistry 5 R,6 R,7 S,13 S,14 S,15 R,16 R. Detailed IN VITRO biological measurements are provided.

Five new steroids, the cholest-4-ene-3,22-diones: tumacone A ( 1 ), tumacone B ( 2 ), tumacoside A ( 3 ), tumacoside B ( 4 ), and a furostenone: tumaquenone ( 5 ), besides diosgenone ( 6 ), were isolated from the aerial parts of Solanum nudum . Their structures were determined by 2D NMR, MS analyses and chemical correlations. Steroid 3 and 5 displayed in vitro antimalarial activity against a Plasmodium falciparum chloroquine-resistant FCB-1 strain (IC 50 27 and 16 μM). The observed stereodependent cyclization into spiroketals of two 16-O isomers is discussed.

Peganum harmala is used in traditional medicine to treat a number of diseases including cancer. Our preliminary studies show that the alkaloidal extract of PH seed is cytotoxic to several tumor cell lines in vitro and has antitumor effect in a tumor model in vivo. The present investigation was aimed at extending our previous studies in identifying the components in P. harmala seed-extract responsible for the cytotoxic effects, and study the cytotoxic and antiproliferative activity of isolated alkaloids and total alkaloidal fraction (TAF) in several tumor cell lines. Four alkaloids: harmalicidine, harmine, peganine (vasicine) and vasicinone were isolated from the P. harmala seed-extract and their activity and that of TAF were tested a) for their cytotoxic activity against four tumor cell lines [three developed by us by chemical-induction in Wistar rats: 1) Med-mek carcinoma ; 2) UCP-med carcinoma ; 3) UCP-med sarcoma] ; and 4) SP2/O-Ag14, and b) for antiproliferative effect on cells of Jurkat, E6-1 clone (inhibition of incorporation of {(3)H-thymidine} in cellular DNA). The alkaloids and TAF inhibited the growth of tumor cell lines to varying degrees; Sp2/O-Ag14 was the most sensitive, with IC50 values (concentration of the active substance that inhibited the growth of the tumor cells by 50%) ranging between 2.43 μg/mL and 19.20 μg/mL, while UCP-med carcinoma was the least sensitive (range of IC50 = 13.83 μg/mL to 59.97 μg/mL). Of the substances evaluated, harmine was the most active compound (IC50 for the 4 tumor cell lines varying between 2.43 μg/mL and 18.39 μg/mL), followed by TAF (range of IC50 = 7.32 μg/mL to 13.83 μg/mL); peganine was the least active (IC50 = 50 μg/mL to100 μg/mL). In terms of antiproliferative effect, vasicinone and TAF were more potent than other substances: the concentration of vasicinone, and TAF needed to inhibit the incorporation of {(3)H-TDR} in the DNA cells of Jurkat, E6-1 clone by 50% (IC50) were 8.60 ± 0.023 μg/mL and 8.94 ± 0.017 μg/mL, respectively, while peganine was the least active (IC50100 μg/mL). The IC50 values for harmalacidine (27.10 ± 0.011 μg/mL) and harmine (46.57 ± 0.011 μg/mL) were intermediate. The harmala alkaloids inhibited the growth of four tumor cell lines, and proliferation of Jurkat cells with varying potencies. Harmine was the most potent in inhibiting cell growth, and vasicinone was most active as antiproliferating substance. The TAF had significant cytotoxic as well as antiproliferating activity.

From the bark of Combretum nigricans , four pentacyclic triterpenes have been isolated and their structures elucidated from spectral data as the known arjungenin and arjunglucoside, a new pentacyclic triterpene, combregenin (2α,3β,6β,19α,23-pentahydroxyolean-12-en-28-oic acid) and a new saponin, combreglucoside (β- d -glucopyranosyl 2α,3β,6β,19α,23-pentahydroxyolean-12-en-28-oate).

From the broth culture of the fungal pathogen Hypoxylon mammatum responsible for canker in aspen (Populus species) two new phytotoxins, hymatoxins K (2) and L (3), diterpenoid α-D-manno-pyranosides were isolated and their structures determined by mass spectrometry and 2D-NMR.

Combreglutinin [4], a hydrolyzable tannin, was isolated from the leaves of Combretum glutinosum, and its macrocyclic structure was established on the basis of 1 H- and 13 C-nmr and 2D nmr spectroscopic data and by chemical methods. The three known tannins 2,3-(S)-hexahydroxydiphenoyl-D-glucose [1], punicalin [2], and punicalagin [3] were also isolated

DNA topoisomerases, enzymes involved in DNA replication and transcription, are known as targets for anticancer drugs. Among the various types of topoisomerase inhibitors, flavones (F) have been identified as promising compounds. In this study, it is shown that the potency of flavones acting as topoisomerase I inhibitors can be ranked according to their redox properties and their 3D structure. Linear correlations were observed between the topoisomerase I inhibition activity exerted by five flavones (chrysin, apigenin, kaempferol, fisetin, quercetin) and experimental and theoretical redox parameters of F. Moreover, theoretical calculations of the dihedral angle O(1)-2-1'-2' in the flavone molecules indicate the importance of their structural and steric features in their potency as topoisomerase I inhibitors. It is suggested that the flavones might interact with the DNA-topoisomerase I complex after their oxidation into quinones via autoxidation, enzymatic oxidation, or reactions with reactive oxygen species. Our investigation opens a new strategy quantitatively based on redox and 3D structural parameters in the search for the most active flavones as anticancer drug candidates inhibiting topoisomerase I.

A new pyrrolidine alkaloid, bgugaine, 1 was isolated along with irniine, 2, from Arisarum vulgare tubers and its structure elucidated by 1H and 13C 2D-COSY NMR techniques. The antibiotic and antifungal properties of both alkaloids were investigated. They exhibited inhibitory effects on the growth of Gram-positive bacteria, yeasts and some filamentous fungi.

Two new bisindole alkaloids, vingramine (1) and methylvingramine (2), were isolated from the seeds of Catharanthus roseus, Apocynaceae. The structures were determined by HRFABMS as well as one- and...

Three new compounds, prepromalabaricone B ( 1 ) and two dimeric acylphenols, giganteones A ( 2 ) and B ( 3 ) were isolated from EtOAc extract of the fruits of Myristica gigantea (Myristicaceae), together with known promalabaricone C ( 4 ), malabaricones A–C ( 5–7 ) and maingayone ( 8 ). The structures were determined by mass and 2D NMR spectral analysis, and the enzymatic synthesis of giganteones A and B was performed from malabaricone C. Both 2 and 3 possess significant cytotoxic activity in vitro against human nasopharynx KB cells.

Two new alkaloids, dehydronitraramine (1) and N-formylmyrionine (2) were isolated from the leaves of Myrioneuron nutans, and their structures were determined from spectroscopic analysis, including mass spectrometry and 2D-NMR spectroscopy. The absolute configuration 8S, 9R, 10S of N-formylmyrionine (2) was established by N-formylation of the known (8S,9R,10S)-myrionine and then comparison of the optical rotation of the natural N-formylmyrionine (2) with that of the semi-synthetic (8S,9R,10S)-N-formylmyrionine. Dehydronitraramine (1) displayed a moderate antiplasmodial activity against Plasmodiumfalciparum with an IC50 value of 16 μM, whereas both 1 and 2 showed a weak cytotoxicity against KB cells.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Two new alkaloids, dehydronitraramine (1) and N-formylmyrionine (2) were isolated from the leaves of Myrioneuron nutans, and their structures were determined from spectroscopic analysis, including mass spectrometry and 2D-NMR spectroscopy. The absolute configuration 8S, 9R, 10S of N-formylmyrionine (2) was established by N-formylation of the known (8S,9R,10S)-myrionine and then comparison of the optical rotation of the natural N-formylmyrionine (2) with that of the semi-synthetic (8S,9R,10S)-N-formylmyrionine. Dehydronitraramine (1) displayed a moderate antiplasmodial activity against Plasmodiumfalciparum with an IC50 value of 16 μM, whereas both 1 and 2 showed a weak cytotoxicity against KB cells.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The structure of annomontacin [I], a novel monotetrayhydrofuran fatty acid gamma-lactone (acetogenin) isolated from the seeds of Amnona montana, was determined by spectral analysis. The cytotoxicities in vitro of annomontacin [I], annonacinone [2], and annonacin were measured against murine leukemia L1210, human breast adenocarcinoma MDA-MB231, and human breast carcinoma MCF7 cell lines and compared with adriamycin.

From the New Caledonian Xylopia vieillardi, two new isoquinoline alkaloids, dehydroxylopine, a dehydroaporphine, and dehydrocorytenchine, a protoberberine, have been isolated and characterized, in addition to twenty-five known isoquinoline, benzylisoquinoline, aporphinoid, and protoberberine type alkaloids. The structures of the new compounds were determined by spectroscopic analysis. Unambiguous 1 H-nmr assignments of 2,3,10,11-substituted phenolic tetrahydroprotoberberines in CF 3 COOD are also reported

International audience; Two new alkaloids, (5S,9S,10R)-myrionidine (1) and (5S,9S,10R,13S)-myrionamide (2), along with the known schoberine (3), were isolated from the leaves of Myrioneuron nutans (Rubiaceae), and their structures were determined from spectral analysis, including mass spectrometry and 2D NMR. The total asymmetric syntheses of (-)-myrionidine (1), (-)-schoberine (3), their enantiomers as well as their 9-epimers derivatives were performed, allowing the determination of their absolute configuration together with that of myrionamide (2). (-)-Myrionidine (1) and its synthetic enantiomer (18) showed a significant antimalarial activity on Plasmodium falciparum.

Hypaphorine, an alpha-N,N,N-trimethyltryptophan betaine, was isolated, for the first time, from Astragalus lusitanicus Lam. (Fabaceae), a plant highly toxic for lambs and goats. This alkaloid was characterized by NMR and MS analysis. Hypaphorine was previously reported to be a convulsive poison. To confirm the toxicity, it was synthesized and tested in goats. Hypaphorine was shown to be non-toxic for goats even at a high dose of 2 g kg(-1) by oral administration.

A new alkaloid, myrioneurinol ( 1 ), was isolated from the leaves of Myrioneuron nutans and its structure determined from spectral analysis, including mass spectrometry and 2D NMR. Myrioneurinol ( 1 ) presented an unprecedented fused tetracyclic skeleton. The absolute configuration was established by the modified Mosher's method, using ( R )- and ( S )-9-anthrylmethoxyacetic acid (9-AMAA). A plausible biosynthetic pathway starting from l -lysine via Δ-piperideine was proposed for 1 in comparison with nitraramine biosynthesis and related alkaloids.

The structures of annomonicin 1 and montanacin 2 , two novel monotetrahydrofuran fatty acid γ-lactones (acetogenins) isolated from Annona montana (Annonaceae), were determined by spectral analysis. Cytotoxic activities were mesured against L1210, P388 and MDA-MB231 cell lines.

Five new 7-methoxy-flavone 5-O-glycosides were isolated from a cytotoxic MeOH extract of Lethedon tannaensis, and the structures were elucidated by 2D NMR spectral analysis and by chemical methods. Lethedosides A (1), B (2), and C (3) were 5-O-glucosides of 7,3', 4'-tri-O-methylluteolin, 7,3',4',5'-tetra-O-methyltricetin, and 7,3', 4'-tri-O-methytricetin, respectively; lethediosides A (4) and B (5) and a known compound 6 were 5-O-xylosylglucosides of 7,3', 4'-tri-O-methylluteolin, 7,3',4',5'-tetra-O-methyltricetin, and 7, 4'-di-O-methylapigenin, respectively. These flavonoids were either inactive or weakly active against KB tumor cells, in contrast to previously isolated flavones from the same plant.

Amber, fossilized tree resin, found at the Oise River area of the Paris basin (France) was dated as being 55 million years old. Quesnoin, a novel unique pure organic compound, was isolated from Oise amber. 1H and 13C NMR spectroscopic analysis indicated an unknown diterpene skeleton, quesnane. The absolute configurations of the eight chiral centers of quesnoin were determined to be 4S, 5S, 8R, 9S, 10S, 13S, 14R, and 16S by chiral auxiliary (R)- and (S)-phenylglycine methyl ester derivatization. Quesnoin allowed us to disclose the tree producer, corresponding to modern Hymenaea oblongifolia, Fabaceae, a subfamily of Caesalpiniaceae, one of the oldest angiosperm. The presence of the Amazon rainforest tree, H. oblongifolia, indicated that the climate of the Paris basin might have been tropical in the early Eocene period, 55 million years ago.

International audience; Myrionine (1), a new 8beta-alkyl-cis-decahydroquinoline, was isolated from Myrioneuron nutans. Its structure was determined by spectral methods and then confirmed by X-ray analysis and total synthesis. In solution, 1 gives rise to an N-in/N-out equilibrium. The solvent has weak influence on the N-in/N-out ratio for myrionine (1), whereas together with the anions, it plays an important role for myrionine hydrochloride (9) and hydroiodide (10). The two N-in and N-out conformations obtained separately by crystallization of 9 and 10, respectively, were analyzed by X-ray diffraction.

Background The global spread of multidrug–resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s. Methods and Findings Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P. yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory concentration [IC50] 3.1 μM, therapeutic index [TI] 14) and P. falciparum (IC50 4.2 μM, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition being most pronounced during the early developmental stages. One derivative, N-cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was selected for its lower toxicity (IC50 3.3 μM, TI 46, and IC50 42.4 μM, TI 60, on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral administration of NCP-tazopsine completely protected mice from a sporozoite challenge. Unlike the parent molecule, the derivative was uniquely active against Plasmodium hepatic stages. Conclusions A readily obtained semisynthetic derivative of a plant-derived compound, tazopsine, has been shown to be specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug severely restricts the pressure for the selection of drug resistance to a parasite stage limited both in numbers and duration, thus allowing researchers to envisage the incorporation of a true causal prophylactic in malaria control programs., A derivative of a morphinan alkaloid, tazopsine, from a plant used against malaria in Madagascar, is active against the hepatic stages ofPlasmodium species., Editors' Summary Background. The parasite that causes malaria has quickly developed resistance to many of the drugs that are commonly used to treat this disease. As a result, new drugs and drug combinations are needed. In some parts of the world where antimalarial drugs are failing due to resistance, or are not available to everyone, people often turn to traditional herbal remedies instead. These traditional plant remedies can be a useful starting point for development of new drugs, but the process of developing effective new drugs from plant remedies is long and complicated. An important initial step is to isolate and identify the active compounds from plants and then see how well these compounds perform against malaria parasites in laboratory tests. If the tests are successful, such compounds could then progress to experiments in animals and possibly eventually human trials. One plant used widely in Madagascar for treatment of malaria is Strychnopsis thouarsii; the traditional remedy consists of the plant stem bark boiled in water. Why Was This Study Done? The group of researchers doing this study wanted to discover candidates for new malaria drugs. They therefore wanted to find out which molecular compounds in the stem bark of S. thouarsii contained antimalarial activity, and what particular stage of the malaria parasite's life cycle these compounds had an effect on. The researchers suspected that the agents in this plant bark had some activity against the “liver stage” of malaria infection in humans. This is the first stage of infection, after a person has been bitten by a malaria-infected mosquito, and before blood cells are invaded by malaria parasites (which then causes the disease symptoms). Very few drugs currently in existence have an effect on the “liver stage” of infection, but activity at this stage would be tremendously useful because it could mean a drug is better for prevention of malaria than others in existence. What Did the Researchers Do and Find? First, the researchers wanted to take the traditional herbal remedy—of S. thouarsii bark boiled in water—and find out precisely which molecule in that remedy was responsible for the antimalarial activity. They therefore used a method called chromatography to progressively separate the herbal extract into its distinct components. At each stage of separation, the extract was checked for activity against malaria using a laboratory test. Inactive extracts were disregarded, and the active component then taken on to a further separation round. After many rounds of separation and testing, the researchers got down to a single, apparently new, molecule that was active against malaria in the laboratory test, and this molecule was named tazopsine (in the Malagasy language the word Tazo refers to malaria). In order to find out how effective the molecule was at killing malaria parasites, the researchers took human or mouse liver cells cultured in the laboratory, infected them with malaria parasites (either the malaria parasite that normally infects humans, or a related species that infects mice), and then added tazopsine at different concentrations. The compound completely killed the malaria parasites even at very low concentrations, and had activity against malaria infecting either liver cells or red blood cells. Tazopsine was then given to mice injected with a species of the malaria parasite. The compound protected most mice against malaria infection when it was used at a dosage level lower than the toxic dose. The researchers then tried making a series of different variants of tazopsine in the hope that some variants would be less toxic, but equally active as, the original compound. They found one variant, named NCP-tazopsine, that was much less toxic but just as active as tazopsine, but only against the malaria infecting liver cells. What Do These Findings Mean? In these experiments a new molecule, tazopsine, was discovered from a Malagasy plant, and it was found to be active against liver-stage malaria parasites, in laboratory experiments and in mice. This molecule or variants of it could in future become candidate antimalarial drugs in humans. However, much work would need to be done before testing could get to that stage. Different variants of molecules related to tazopsine would need to be tested to find one that has low toxicity, and these variants would need to be fully evaluated in animals to see how they are handled in the body before any trials could begin in humans. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030513 The World Health Organization publishes a minisite containing links to information about all aspects of malaria worldwide, including treatment, prevention, and current programmes for malaria control Medicines for Malaria Venture is a collaboration between public and private organizations (including the pharmaceutical industry) that aims to fund and manage the development of new drugs for treatment and prevention of malaria Wikipedia entries for drug discovery and drug development (note: Wikipedia is an internet encyclopedia that anyone can edit)

A new cyclopeptide alkaloid, mauritine J, besides known alkaloids, was isolated from the root bark of Zizyphus mauritiana. Its structure was established by homo- and hetero-nuclear 2D NMR analysis and compared with that of amphibine E.

The methanolic extract from the leaves of Kalanchoe streptantha (Crassulaceae) afforded a new kaempferol 3-O-β-xylopyranosyl-(1→2)-α-rhamnopyranoside 7-O-(4‘‘‘‘-O-acetyl-α-rhamnopyranoside), named 4‘‘‘‘-acetylsagittatin A (1), and the known sagittatin A (2). The structures were determined by 1H-1H and 1H-13C COSY NMR and FAB mass spectroscopy and confirmed by analysis of the peracetylated derivative.

From ethyl acetate and methanolic extracts of Lethedon tannaensis leaves, which were cytotoxic against murine leukemia (P-388) and human nasopharynx carcinoma (KB) cells, one new and six known 5-hydroxy-7-methoxyflavones variously substituted on the B ring were isolated and their structures determined by spectral analysis. Compounds active against KB cells were velutin (4) (IC50 4.8 microM), 7,3',5'-tri-O-methyltricetin (2) (IC50 22.2 microM), genkwanin (6) (IC50 30.6 microM), and the novel compound, 7,3',4'-tri-O-methyltricetin, named lethedocin (1) (IC50 47.6 microM). These flavones required the presence of hydroxyl groups at C-5 and C-4' and methoxyl groups at C-7 and C-3' for inhibition of calf thymus DNA topoisomerase I activity.

In vitro studies were carried out in rat pleural polymorphonuclear leukocytes (PMNs) activated by opsonized zymosan (OZ) to investigate the effects of aqueous extract from Acacia cyanophylla seeds on superoxide anions generation. PMNs were collected, after induction of an acute inflammatory reaction, by injection in the rat pleural cavity, of a suspension of calcium pyrophosphate (CaPP) crystals (pleurisy with CaPP) or serum (pleurisy with serum). The results obtained indicate that Acacia cyanophylla aqueous seeds extract had, in vitro, a significant stimulatory effect, in a dose dependent manner, on the PMN superoxide anions generation. It also corrected the diminution of superoxide anions production induced by diclofenac pre-treated PMNs. It could be concluded from the results of this study that the stimulatory properties of Acacia cyanophylla seeds aqueous extract may at least be due to the presence of polyphenols such tannins and/or lignins. Further investigations are needed to determine clearly the mechanisms mediating the generation of superoxide radicals in this phenomenon.

A novel Daphniphyllum alkaloid, daphcalycine (1), was isolated together with known daphnicyclidin D (2) from the stem bark of Daphniphyllum calycinum. The highly condensed polycyclic structure, established by spectral analysis, possessed an unusual framework: a central quinuclidine like tricycle produced by fusion of a piperidine, a tetrahydropyran, and an oxazine ring in turn condensed to surrounding three penta-, one hexa-, and one hepta-membered rings. The relative configuration of 11 carbon stereocenters of 1 was elucidated on the basis of NOESY.

Four new cephalotaxus alkaloids, cephalotaxine alpha-N-oxide (1), cephalotaxine beta-N-oxide (2), 11-beta-hydroxycephalotaxine beta-N-oxide (3), and isocephalotaxine (4), were isolated, together with several known alkaloids from an EtOAc extract of the fruits of Cephalotaxus fortunei. The structures were determined by spectral analysis including mass spectrometry and 2D NMR. Compounds 1, 2, 3, and 4 displayed cytotoxicity against nasopharynx KB cells with IC50 values of 30, 14, 31, and 15 micro g/mL, respectively.

Two new epimeric tricyclic alkaloids, myrioxazines A and B were isolated from the leaves of Myrioneuron nutans and their structures elucidated by spectral analysis (mass spectrometry and 2D NMR). Absolute configurations were determined by total asymmetric synthesis.

Two new bisindole alkaloids, vingramine (1) and methylvingramine (2), were isolated from the seeds of Catharanthus roseus, Apocynaceae. The structures were determined by HRFABMS as well as one- and two-dimensional NMR experiments. They possess a new bisindole skeleton involving an indole alkaloid part B with loss of 5',6'-ethylene, a C7'-C16' linkage, a 14'-O-19'-tetrahydrofuran, and a N-4'-isobutyramide group. The 12-methyl vincorine part A and part B are connected via an 11,10'-biphenyl linkage. The relative configuration was determined by NMR analysis. Biogenetic considerations suggested a rearrangement and a double fragmentation at C6'/C7' and N4'/C5' for the formation of 1 from strictamine, further allowing deduction of the absolute configuration of 10 stereocenters: 2S, 7R, 15R, 16R, 3'R, 14'S, 15'S, 16'R, 19'S, and 20'R. The alkaloids 1 and 2 display, in vitro, cytotoxic activity against nasopharynx carcinoma KB cells, IC(50) 5 and 6mgr;M (4 and 5mgr;g/mL).

A toxic pyrrolidine alkaloid, irniine [1], was isolated from Arisarum vulgare tubers, and its structure was elucidated by 2D COSY spectroscopic methods

From the cytotoxic AcOEt extract of the fruits of Myristica maingayi, a Myristicaceae, five new acylphenols (promalabaricones B and C, maingayic acids B and C, and maingayone) were isolated, together with the known malabaricones A–C. The structures were determined from spectral analysis, including mass spectrometry and 2D NMR. The cytotoxicity of the new compounds and that of malabaricones was assessed against KB cells. A biosynthetic pathway for malabaricones, via the corresponding promalabaricones as precursors, is suggested.

Monterine 1 as well as granjine 3, 1R,1'S configured biphenylic bisbenzylisoquinoline alkaloids, generate two highly populated conformers. The interconversion of two forms was detected by saturation tranfer in (1)H NMR NOEs experiments. Tridimensional structure of the conformers was determined on the basis of (1)H NMR analysis of anisotropic shielding protons, by NOEs measurements and vicinal proton coupling constants of CH1-CH(2)alpha and CH1'-CH(2)alpha'. The structures established from NMR data were further refined to observe the mobility of 3D conformations by molecular dynamics simulation in vacuo. The highly populated conformers, monterine 1a and 1b, as well as granjine 3a and 3b, are interconvertible by rotation about the C1'-Calpha', Calpha'-C9', and C11'-C11 bonds and inversion of the benzyl D ring by reference to CH(2)alpha'. The slow exchange system was investigated by dynamic NMR spectroscopy: DeltaG()(c) 77.9 KJ/mol and k(c) 200 s(-)(1) for monterine 1; DeltaG()(c) 77.7 KJ/mol and k(c) 211 s(-)(1) for granjine 3. Natural and synthetic biphenylic bisbenzylisoquinolines displayed, in vitro, cytotoxic activities against human prostate and breast cancer cell lines.

The fractionation of the juice of fresh stems and leaves of Kalanchoe brasiliensis was monitored by an assay measuring lymphocyte proliferative activity and allowed the isolation and identification of seven patuletin rhamnoside derivatives [1-7]. Three of them are novel, namely, patuletin 3-O-(4"-O-acetyl-alpha-L-rhamnopyranosyl)-7-O-(2'"-O-acetyl- alpha-L-rhamnopyranoside) [1], patuletin 3-O-alpha-L-rhamnopyranosyl-7-O-(2'"-O-acetyl-alpha-L- rhamnopyranoside) [3], and patuletin 3-O-(4"-O-acetyl-alpha-L-rhamnopyranosyl)-7-O- rhamnopyranoside [4], and four are known [2, 5-7]. Their structures were determined by the analysis of 1H-1H and 1H-13C COSY nmr, ci, and fab mass spectra.

The cinnamylrutinosides, cinnamrutinoses A and B, were isolated along with known phenolic glucosides, from the stem bark of Populus tremula infected with the pathogenic fungus Hypoxylon mammatum. The structures were determined from spectroscopic and chemical evidence.