Showing papers in "Journal of Natural Products in 2002"

Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: a drug discovery effort against Alzheimer's Disease

Abstract: From Curcuma longa, two novel compounds, 4' '-(3' "-methoxy-4' "-hydroxyphenyl)-2' '-oxo-3' '-enebutanyl 3-(3'-methoxy-4'hydroxyphenyl)propenoate (calebin-A, 1) and 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one (2), and seven known compounds, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (curcumin, 3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (demethoxycurcumin, 4), 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (bisdemethoxycurcumin, 5), 1-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-6-heptene-3,5-dione (6), 1,7-bis(4-hydroxyphenyl)-1-heptene-3,5-dione (7), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (8), and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one (9), were isolated following a bioassay-guided fractionation scheme utilizing an assay to detect protection of PC12 cells from beta-amyloid insult. Compounds 1, 3-5, and 7 were found to more effectively protect PC12 cells from betaA insult (ED(50) = 0.5-10 microg/mL) than Congo red (10) (ED(50) = 37-39 microg/mL).

Isolation and Structure Elucidation of Radical Scavengers from Thymus vulgaris Leaves

Abstract: 2,2-Diphenyl-1-picrylhydrazyl radical (DPPH•) scavenging activity-guided fractionation of a leaf extract of Thymus vulgaris led to the isolation of the radical scavengers rosmarinic acid 1, eriodictyol, taxifolin, luteolin 7-glucuronide, p-cymene 2,3-diol, p-cymene 2,3-diol 6−6‘-dimer, carvacrol, thymol, and a new compound, 2. The fractionation was considerably facilitated by using an on-line HPLC detector for radical scavenging activity. In this detector activity is monitored as the disappearance of the color of a postcolumn added stable radical after reacting with radical scavengers in a reaction coil. Compound 2, which consists of rosmarinic and caffeic acid moieties linked via a C-3‘−C-8‘ ‘ ether bridge, was mainly elucidated by various NMR techniques and CD. Phenylpropanoid trimer 2 was a weaker and stronger radical scavenger than rosmarinic acid 1 in off-line TEAC and DPPH• assays, respectively.

Novel 12-Deoxy-16-hydroxyphorbol Diesters Isolated from the Seed Oil of Jatropha curcas

Abstract: Six unstable intramolecular diterpene esters were isolated from the seed oil of Jatropha curcas. Five of these, Jatropha factors C2−C6 (3−7), are new natural products, and the structure of the known Jatropha factor C1 (2) has been revised. All compounds possess the same diterpene moiety, namely, 12-deoxy-16-hydroxyphorbol (1). The dicarboxylic acid moieties of 2−5 contain a bicyclo[3.1.0]hexane unit, and those of 6 and 7 a cyclobutane unit, which is described for the first time within this compound class. Compounds 4 and 5 are C-8‘ epimers. The structures of 2−7 were elucidated by spectroscopic methods and give an insight into the biogenesis of the characterized substances.

New Chemical Constituents of Euphorbia quinquecostata and Absolute Configuration Assignment by a Convenient Mosher Ester Procedure Carried Out in NMR Tubes

Abstract: Two new compounds, an ent-isopimarane-type diterpene, 3alpha,12alpha-dihydroxy-ent-8(14),15-isopimaradien-18-al (1), and a dihydrobenzo[b]furan neolignan, (-)-trans-9-acetyl-4,9'-di-O-methyl-3'-de-O-methyldehydrodiconiferyl alcohol (2), along with five known compounds, 7,7'-dihydroxy-6,8'-bicoumarin (bicoumol) (3), 3,4-dimethoxycinnamaldehyde (4), 6-hydroxy-7-methoxycoumarin (isoscopoletin), N-butylaniline, and vanillin, have been isolated from an ethyl acetate-soluble extract of the stem wood of Euphorbiaquinquecostata. The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic data interpretation, and single-crystal X-ray diffraction analysis was used to confirm the structure and relative stereochemistry of 1. The absolute configuration of 1 was established by a convenient Mosher ester procedure in which the sample was treated with MTPA chlorides in deuterated pyridine directly in NMR tubes. All isolates were evaluated for the induction of quinone reductase in Hepa1c1c7 hepatoma cells and for the inhibition of the transformation of murine epidermal JB6 cells.

Antimicrobial Activities of Naphthazarins from Arnebia euchroma

Abstract: Bioassay-directed fractionation of extract of Arnebia euchroma led to the isolation of alkannin (1), shikonin (2), and their derivatives (3−8) as the active principles against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The stereochemistry of α-methylbutyryl alkannin (8) is revealed for the first time, and the antimicrobial activity of 8 was compared with its corresponding diastereomer (9). The derivatives 3−9 showed stronger anti-MRSA activity [minimum inhibitory concentrations (MICs) ranged from 1.56 to 3.13 μg/mL] than alkannin or shikonin (MIC = 6.25 μg/mL). Anti-MRSA activity of derivatives was bactericidal with minimum bactericidal concentration (MBC)/MIC ≤ 2. In a time-kill assay, the bactericidal activity against MRSA was achieved as rapidly as 2 h. The derivatives 3−9 were also active against vancomycin-resistant Enterococcus faecium (F935) and vancomycin-resistant Enterococcus faecalis (CKU-17) with MICs similar to those with MRSA. Aromatic este...

In Vitro Cytotoxic Activity of Phenanthroindolizidine Alkaloids from Cynanchum vincetoxicum and Tylophora tanakae against Drug-Sensitive and Multidrug-Resistant Cancer Cells

Abstract: Two known phenanthroindolizidine alkaloids, (-)-(R)-13aalpha-antofine (1) and (-)-(R)-13aalpha-6-O-desmethylantofine (2), and two new natural products, (-)-(R)-13aalpha-secoantofine (3) and (-)-(R)-13aalpha-6-O-desmethylsecoantofine (4), were isolated from Cynanchum vincetoxicum. The structures of all compounds were established by means of NMR methods including COSY, NOESY, HSQC, and HMBC experiments, supported by HRMS and optical rotation data. Cytotoxic activity of the isolated alkaloids, and of three other alkaloids previously isolated from Tylophora tanakae, (-)-(R)-13aalpha-tylophorine (5), (-)-(R)-13aalpha-7-O-desmethyltylophorine (6), and (+)-(S)-13abeta-isotylocrebrine (7), was assessed in vitro using a drug-sensitive KB-3-1 and a multidrug-resistant KB-V1 cancer cell line. Structure-activity relationships in this series of alkaloids are discussed. The IC(50) values of some of the alkaloids are in the low nanomolar range, being thus comparable to the activity of clinically used cytotoxic drugs. Previously reported adverse side effects of these alkaloids could possibly be overcome by modern tissue-specific drug targeting techniques.

Choosing the Best Pulse Sequences, Acquisition Parameters, Postacquisition Processing Strategies, and Probes for Natural Product Structure Elucidation by NMR Spectroscopy

Abstract: The relative merits of different pairs of two-dimensional NMR pulse sequences (COSY-90 vs COSY-45, NOESY vs T-ROESY, HSQC vs HMQC, HMBC vs CIGAR, etc.) are compared and recommendations are made for the preferred choice of sequences for natural product structure elucidation. Similar comparisons are made between different selective 1D sequences and the corresponding 2D sequences. Many users of 2D NMR use longer than necessary relaxation delays and neglect to use forward linear prediction processing. It is shown that using shorter relaxation delays in combination with forward linear prediction allows one to get better resolved spectra in less time. The relative merits of different probes and likely future probe developments are also discussed.

Structure and absolute stereochemistry of hectochlorin, a potent stimulator of actin assembly.

Abstract: Hectochlorin (1) was isolated from marine isolates of Lyngbya majuscula collected from Hector Bay, Jamaica, and Boca del Drago Beach, Bocas del Toro, Panama. The planar structure was deduced by one- and two-dimensional NMR spectroscopy. X-ray crystallography was used to determine the absolute stereochemistry of hectochlorin as 2S,3S,14S,22S. Hectochlorin is equipotent to jasplakinolide (5) in its ability to promote actin polymerization, but unlike jasplakinolide, is unable to displace a fluorescent phalloidin analogue from polymerized actin. In addition, hectochlorin shows both a unique profile of cytotoxicity by the COMPARE algorithm and potent inhibitory activity toward the fungus Candida albicans. Structurally, hectochlorin resembles dolabellin and the recently reported lyngbyabellin class of compounds.

Bioactive metabolites from a marine-derived strain of the fungus Emericella variecolor.

Abstract: From a marine-derived strain of the fungus Emericella variecolor, varitriol (1), varioxirane (2), dihydroterrein (3), and varixanthone (4), besides the known mold metabolites ergosterol, terrein, shamixanthone, and tajixanthone hydrate, were identified. The chemical structures of 1-4 were established by means of spectroscopic techniques and some chemical transformations. In the NCI's 60-cell panel, varitriol (1) displayed increased potency toward selected renal, CNS, and breast cancer cell lines. Varixanthone (4) showed antimicrobial activity.

Antiinflammatory Constituents of Celastrus orbiculatus Inhibit the NF-κB Activation and NO Production

Abstract: Two new sesquiterpene esters, 1β,8β-diacetoxyl-6α,9α-difuroyloxydihydro-β-agarofuran (1) and 1β-acetoxyl-2β,6α,9α-trifuroyloxydihydro-β-agarofuran (2), together with four known sesquiterpene esters (3−6), celastrol (7), and celaphanol A (8) were isolated from the roots of Celastrus orbiculatus in a search for inhibitors of NF-κB activation and nitric oxide production. Compound 7 was the most active, while compounds 1, 2, 4, and 8 showed moderate inhibition in both NF-κB activation and nitric oxide production.

New metabolites from sponge-derived fungi Curvularia lunata and Cladosporium herbarum.

Abstract: The fungus Curvularia lunata, isolated from the marine sponge Niphates olemda, yielded the new 1,3,8-trihydroxy-6-methoxyanthraquinone, which we named lunatin (1), the known modified bisanthraquinone cytoskyrin A (2), and the known plant hormone (+)-abscisic acid (3). Both anthraquinones were found to be active against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. Two strains of the fungus Cladosporium herbarum, isolated from the sponges Aplysina aerophoba and Callyspongia aerizusa, respectively, yielded two new α-pyrones, herbarin A (4) and herbarin B (5), the known compound citreoviridin A (6), and the new phthalide herbaric acid (7). All structures were unambiguously established by 1D and 2D NMR and MS data.

Lignans Isolated from Valerian: Identification and Characterization of a New Olivil Derivative with Partial Agonistic Activity at A1 Adenosine Receptors

Abstract: A methanolic extract of the roots of Valeriana officinalis (valerian) was investigated for its lignan content. In addition to the lignans 8‘-hydroxypinoresinol (1) and pinoresinol-4-O-β-d-glucoside (2), which had already been isolated from valerian in an earlier study, the 7,9‘-monoepoxylignans massoniresinol-4‘-O-β-d-glucoside (3), 4‘-O-β-d-glucosyl-9-O-(6‘ ‘-deoxysaccharosyl)olivil (4), and berchemol-4‘-O-β-d-glucoside (5) and the 7,9‘:7‘,9-diepoxylignans pinoresinol-4,4‘-di-β-O-d-glucoside (6), 8-hydroxypinoresinol-4‘-O-β-d-glucoside (7), and 8‘-hydroxypinoresinol-4‘-O-β-d-glucoside (8) were identified. While lignans 3, 6, 7, and 8 had already been isolated from other plants, lignans 4 and 5 are new natural products. The lignans were investigated in radioligand binding assays at various receptors of the central nervous system, including GABAA, benzodiazepine, 5-HT1A, and adenosine A1 and A2A receptors, to investigate their potential contribution to the pharmacological activity of valerian. The novel ol...

Aromatase inhibitors from Broussonetia papyrifera

Abstract: A composition and method of cancer treatment is disclosed. The composition and method utilize the extract of B. papyrifera, or compounds included therein having aromatase inhibition properties, as active cancer chemopreventative and treating agents in mammals, including humans.

Antifungal stilbenoids from Stemona collinsae.

Abstract: Fifteen new stilbenoids including 11 phenylbenzofurans, the stemofurans A−K (1−11), and four dihydrostilbenes, the stilbostemins A (15), C (17), E (19), and F (20), were isolated and identified from a methanolic extract of Stemona collinsae roots together with five known derivatives, the stilbenes pinosylvin (13) and 4‘-methylpinosylvin (14), the dihydrostilbenes, stilbostemins B (16) and D (18), and the dihydrophenanthrene racemosol (12) as well as (+)-sesamin, coniferyl alcohol, and stigmasterol. Bioautographic tests with Cladosporium herbarum displayed antifungal activity for stilbenoids of all four structural types. Ten derivatives were tested against five microfungi using the microdilution technique linked with digital image analysis of germ tubes.

Pachastrissamine, a cytotoxic anhydrophytosphingosine from a marine sponge, Pachastrissa sp.

Abstract: An anhydrophytosphingosine named pachastrissamine (3) has been isolated as a cytotoxic principle of a sponge, Pachastrissa sp., and the structure including the absolute configuration determined by spectroscopic and chemical analysis.

Differentiation- and Apoptosis-Inducing Activities by Pentacyclic Triterpenes on a MOuse Melanoma Cell Line

Abstract: In a study to investigate the relationship between the chemical structure and the differentiation-inducing activity of pentacyclic triterpenes, several lupane, oleanane, and ursane triterpenes were prepared and their effects on B16 2F2 melanoma cell differentiation and growth were examined. Eleven lupane triterpenes used in this study acted on the melanoma cells as a melanogen, but no induction of melanogenesis of B16 2F2 cells by oleanane and ursane was detected. The differences at C-17 of the lupane series and acetylation of the OH group at C-3 did not markedly influence their activities. However, the ED(50) value for up-regulation of melanin biosynthesis was markedly decreased by the oxidation of the OH group at C-3 of lupeol (1). Betulinic acid (11), its methyl ester (12), lup-28-al-20(29)-ene-3beta-ol (9), and lup-28-al-20(29)-en-3-one (10) inhibited B16 2F2 cell proliferation by induction of apoptosis. These findings suggested that the carbonyl group at C-17 might be essential for the apoptotic effects of these compounds on B16 2F2 cells.

Monoterpene Hydroperoxides with Trypanocidal Activity from Chenopodium ambrosioides

Abstract: Four monoterpene hydroperoxides were isolated from aerial parts of Chenopodium ambrosioides along with ascaridole (1), the anthelmintic principle of this plant, as anti-trypanosomal compounds. The structures of these monoterpenes were determined to be (-)-(2S,4S)- and (-)-(2R,4S)-p-mentha-1(7),8-dien-2-hydroperoxide (2a and 3a) and (-)-(1R,4S)- and (-)-(1S,4S)-p-mentha-2,8-dien-1-hydroperoxide (4a and 5a) on the basis of spectroscopic methods and chemical correlations. In vitro trypanocidal activities of ascaridole (1) and these hydroperoxides (2a-5a) against epimastigotes of Trypanosoma cruzi were 23, 1.2, 1.6, 3.1, and 0.8 microM, respectively. Fresh leaves of C. ambrosioides also contained isomeric hydroperoxides 6a and 7a, and the content ratio of 2a-7a suggested that these hydroperoxides were formed through the singlet-oxygen oxidation of limonene.

New polyhydroxylated pyrrolidine, piperidine, and pyrrolizidine alkaloids from Scilla sibirica.

Abstract: Chromatographic separation of an extract of the bulbs of Scilla sibirica resulted in the isolation of five pyrrolidines, two pyrrolidine glycosides, six piperidines, one piperidine glycoside, and eight pyrrolizidines. 2,5-Dideoxy-2,5-imino-glycero-d-manno-heptitol (homoDMDP, 1) is a common alkaloid in all plants of the Hyacinthaceae examined to date and was also found in S. sibirica. The structures of the new alkaloids were elucidated by spectroscopic methods as 7-deoxy-homoDMDP (4), 2,5-dideoxy-2,5-imino-glycero-d-galacto-heptitol (5), the 4-O-beta-d-mannoside (6) and the 4-O-beta-d-mannobioside (7) of 6-deoxy-homoDMDP (2), 7-deoxyhomonojirimycin (12), 7-deoxyhomomannojirimycin (13), and polyhydroxypyrrolizidines, hyacinthacines A(4) (15), A(5) (16), A(6) (17), A(7) (18), B(4) (20), B(5) (21), and B(6) (22). HomoDMDP (1) is a potent inhibitor of beta-glucosidase and beta-galactosidase, while 6-deoxy-homoDMDP (2) showed significantly less inhibition. However, 7-deoxygenation of 1, leading to 4, showed no effect on the inhibitory activity toward both enzymes. Although 2 is not an inhibitor of alpha-l-fucosidase, the monomannoside of 2 shows inhibitory activity toward alpha-l-fucosidase. Elongation of the beta-mannopyranosyl chain of 6 to give 7 enhanced the inhibitory activity.

Novel Bioactive Clerodane Diterpenoids from the Leaves and Twigs of Casearia sylvestris

Abstract: Fractionation of a methanol extract of the leaves and twigs of Casearia sylvestris, as directed by activity against KB cell cytotoxicity, led to the isolation of three novel clerodane diterpenoids, casearvestrins A-C (1-3). The structures of 1-3 were deduced from one- and two-dimensional NMR experiments, including relative stereochemical assignments based on ROESY correlations and COSY coupling constants. All three compounds displayed promising bioactivity, both in cytotoxicity assays against a panel of tumor cell lines and in antifungal assays via the growth inhibition of Aspergillus niger in a disk diffusion assay.

Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive activity.

Abstract: Activity-guided fractionation of an ethyl acetate extract of the aerial parts of Tithonia diversifolia, using an antiproliferation bioassay performed with human colon cancer (Col2) cells, led to th...

Constituents of the bark and twigs of Artocarpus dadah with cyclooxygenase inhibitory activity.

Abstract: Fractionation of an ethyl acetate-soluble extract of the bark of Artocarpus dadah has led to the isolation of three new prenylated stilbenoid derivatives, 3-(γ,γ-dimethylallyl)resveratrol (1), 5-(γ,γ-dimethylallyl)oxyresveratrol (2), 3-(2,3-dihydroxy-3-methylbutyl)resveratrol (3), and a new benzofuran derivative, 3-(γ,γ-dimethylpropenyl)moracin M (4), along with six known compounds, oxyresveratrol, (+)-catechin, afzelechin-3-O-α-l-rhamnopyranoside, (−)-epiafzelechin, dihydromorin, and epiafzelechin-(4β→8)-epicatechin. From an ethyl acetate-soluble extract of the twigs of the same plant were isolated compound 4 and two new neolignan derivatives, dadahols A (5) and B (6), as well as 10 known compounds, oxyresveratrol, (+)-catechin, afzelechin-3-O-α-l-rhamnopyranoside, resveratrol, steppogenin, moracin M, isogemichalcone B, gemichalcone B, norartocarpetin, and engeletin. The structures of compounds 1−6 were determined using spectroscopic and chemical methods. Isolates were evaluated for their inhibitory effe...

Plant-like biosynthetic pathways in bacteria: from benzoic acid to chalcone.

Abstract: Although phenylpropanoids and flavonoids are common plant natural products, these major classes of biologically active secondary metabolites are largely absent from bacteria. The ubiquitous plant e...

New antiinfective and human 5-HT2 receptor binding natural and semisynthetic compounds from the Jamaican sponge Smenospongia aurea.

Abstract: In addition to the sesquiterpene-phenol aureols (1), 6‘-chloroaureol (2), and aureol acetate (3), eight indole alkaloids including the new N-3‘-ethylaplysinopsin (9) have been isolated from the Jamaican sponge Smenospongia aurea. Makaluvamine O (10), a new member of the pyrroloiminoquinone class, was also isolated. The structures were characterized by spectroscopic methods, and two new derivatives of aureol were prepared to optimize the biological activity. Aureol N,N-dimethyl thiocarbamate (1a) and 6-bromoaplysinopsin (7) exhibit significant antimalarial and antimycobacterial activity in vitro. Compound 6 showed activity against the Plasmodium enzyme plasmepsin II. The 6-bromo-2‘-de-N-methylaplysinopsin (6), 6-bromoaplysinopsin (7), and N-3‘-ethylaplysinopsin (9) displaced high-affinity [3H]antagonist ligands from cloned human serotonin 5-HT2 receptor subtypes, whereas the other compounds tested did not. Remarkably, the 6-bromo-2‘-de-N-methylaplysinopsin (6) showed a >40-fold selectivity for the 5-HT2C s...

Online analysis of xestodecalactones A-C, novel bioactive metabolites from the fungus Penicillium cf. montanense and their subsequent isolation from the sponge Xestospongia exigua.

Abstract: Fungal isolates of Penicillium cf. montanense were obtained from the marine sponge Xestospongia exigua collected from the Bali Sea, Indonesia. Culture filtrates of the fungi yielded three novel decalactone metabolites, xestodecalactones A, B, and C (1, 2a, and 2b), consisting of 10-membered macrolides with a fused 1,3-dihydroxybenzene ring. Online HPLC-NMR, ESI-MS/MS, and -CD spectra were acquired, and the structures of the new compounds were established and confirmed on the basis of offline NMR spectroscopic (1H, 13C, COSY, ROESY, 1H-detected direct and long-range 13C−1H correlations) and mass spectrometric (EIMS) data. Quantum chemical calculations of the CD spectra proved to be difficult because of the conformational flexibility of the xestodecalactones. These compounds, of which 2a and 2b, due to the additional stereocenter at C-9, are diastereomeric compounds, are structurally related to a number of biologically active metabolites found in terrestrial fungal strains. Compound 2a was found to be activ...

Xanthones from the green fruit hulls of Garcinia mangostana.

Abstract: Three new xanthones, mangostenol (1), mangostenone A (2), and mangostenone B (3), were isolated from the green fruit hulls of Garcinia mangostana, along with the known xanthones, trapezifolixanthone, tovophyllin B (4), α- and β-mangostins, garcinone B, mangostinone, mangostanol, and the flavonoid epicatechin The structures of the new xanthones were elucidated by analysis of their spectroscopic data

New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata

Abstract: Three new monotetrahydrofuran annonaceous acetogenins, muricin H (1), muricin I (2), and cis-annomontacin (3), along with five known acetogenins, annonacin, annonacinone, annomontacin, murisolin, and xylomaticin, were isolated from the seeds of Annona muricata. Additionally, two new monotetrahydrofuran annonaceous acetogenins, cis-corossolone (4) and annocatalin (5), together with four known ones, annonacin, annonacinone, solamin, and corossolone, were isolated from the leaves of this species. The structures of all new isolates were elucidated and characterized by spectral and chemical methods. These new acetogenins exhibited significant activity in in vitro cytotoxic assays against two human hepatoma cell lines, Hep G(2) and 2,2,15. Compound 5 showed a high selectivity toward the Hep 2,2,15 cell line.

New loliolide derivatives from the brown alga Undaria pinnatifida.

Abstract: Seven carotenoid metabolites including five loliolide derivatives have been isolated from the brown alga Undaria pinnatifida, including three new compounds. Structures of these compounds were confirmed by spectroscopic analyses and literature data.

Four new bromotryptamine derivatives from the marine bryozoan Flustra foliacea.

Abstract: Ten brominated alkaloids, 6-bromo-2-(1,1-dimethyl-2-propenyl)-1H-indole-3-carbaldehyde (1), N-(2-[6-bromo-2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]ethyl)-N-methylmethanesulfonamide (2), deformylflustrabromine (3), flustrabromine (4), (3aR,8aS)-6-bromo-3a-[(2E)-3,7-dimethyl-2,6-octadienyl]-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]-indol-7-ol (5), flustramine C (6), dihydroflustramine C (7), flustramine A (8), flustramine D (9), and flustraminol A (10), and the diterpene 4,6-bis(4-methylpent-3-en-1-yl)-6-methylcyclohexa-1,3-diene-carbaldehyde (11) were isolated from the dichloromethane extract of the North Sea bryozoan Flustra foliacea. Of the 10, four (1, 2, 3, and 5) represent new natural products. The structures of all isolates were elucidated by interpretation of their spectroscopic data (NMR, MS, UV, and IR). For compound 4 complete (13)C NMR data are reported for the first time. Compounds 3 and 6-8 were tested on voltage-activated potassium and sodium channels. Flustramine A (8) shows an unspecific blocking activity on Kv1.4 potassium-mediated currents.

Antiplasmodial activity of alkaloids from various strychnos species.

Abstract: The in vitro antiplasmodial activities of 69 alkaloids from various Strychnos species were evaluated against chloroquine-resistant and chloroquine-sensitive lines of Plasmodium falciparum. The compounds, comprising mainly indolomonoterpenoid alkaloids, exhibited a wide range of biological potencies in the antiplasmodial assays. The most active alkaloids were also tested for cytotoxicity against HCT-116 colon cancer cells to determine their antiplasmodial selectivity. As a result of these studies, structure−activity relationships for these alkaloids have begun to emerge. Alkaloids presenting four types of bisindole skeleton exhibited potent and selective activities against Plasmodium. They were sungucine-type (IC50 values ranging from 80 nM to 10 μM), longicaudatine-type (IC50 values ranging from 0.5 to 10 μM), matopensine-type (IC50 values ranging from 150 nM to 10 μM), and usambarine-type alkaloids. Within the last structural type, isostrychnopentamine (49) and ochrolifuanine A (46) were found to be acti...

New seco-prezizaane-type sesquiterpenes, jiadifenin with neurotrophic activity and 1,2-dehydroneomajucin from Illicium jiadifengpi.

Abstract: Two new seco-prezizaane-type sesquiterpenes, 1,2-dehydroneomajucin (1) and jiadifenin (2), were isolated from the methanol extract of the pericarps of Illicium jiadifengpi, indigenous to the southern part of China. Their structures were elucidated on the basis of NMR data. Compound 2, which is an equilibrated mixture of the epimers 2a and 2b on the C-10 acetal carbon, is the first example of a majucin-type seco-prezizaane with an oxo-function at the C-10 position. The proposed structure for 2 was unambiguously confirmed by chemical conversion of the known sesquiterpene (2S)-hydroxy-3,4-dehydroneomajucin (5) to 2. Compounds 2 and 5 were found to significantly promote neurite outgrowth in primary cultures of fetal rat cortical neurons at concentrations from 0.1 to 10 μM.