Showing papers in "Journal of Natural Products in 2005"

Alkaloids from amphibian skin: a tabulation of over eight-hundred compounds.

Abstract: A diverse array of biologically active, lipid-soluble alkaloids have been discovered in amphibian skin. Such alkaloids include the following: the steroidal samandarines from salamanders, the batrachotoxins, histrionicotoxins, gephyrotoxins, and epibatidine from neotropical poison frogs (Dendrobatidae), the pumiliotoxins, allopumiliotoxins, homopumiliotoxins, and decahydroquinolines from certain genera of anurans from four families (Dendrobatidae, Mantellidae, Bufonidae, and Myobatrachidae), a variety of izidines (pyrrolizidines, indolizidines, quinolizidines, lehmizidines), pyrrolidines, piperidines, various tricyclics (related in structures to the coccinellines), and spiropyrrolizidines from the first three of these four families, the pseudophrynamines from one genus of Australian frogs, and a variety of unclassified alkaloids as yet of undetermined structure. With the exception of the samandarines and the pseudophrynamines, all alkaloids appear to be derived from dietary sources. Although only a few of...

Quantitative 1H NMR: development and potential of a method for natural products analysis.

Abstract: Based on a brief revision of what constitutes state-of-the-art “quantitative experimental conditions” for 1H quantitative NMR (qHNMR), this comprehensive review contains almost 200 references and covers the literature since 1982 with emphasis on natural products. It provides an overview of the background and applications of qHNMR in natural products research, new methods such as decoupling and hyphenation, and analytical potential and limitations, and compiles information on reference materials used for and studied by qHNMR. The dual status of natural products, being single chemical entities and valuable biologically active agents that need to be purified from complex matrixes, results in an increased analytical demand when testing their deviation from the singleton composition ideal. The outcome and versatility of reported applications lead to the conclusion that qHNMR is currently the principal analytical method to meet this demand. Considering both 1D and 2D 1H NMR experiments, qHNMR has proved to be h...

Metabolomics reviewed: a new "omics" platform technology for systems biology and implications for natural products research

Abstract: Metabolomics is the study of global metabolite profiles in a system (cell, tissue, or organism) under a given set of conditions. The analysis of the metabolome is particularly challenging due to the diverse chemical nature of metabolites. Metabolites are the result of the interaction of the system's genome with its environment and are not merely the end product of gene expression but also form part of the regulatory system in an integrated manner. Metabolomics has its roots in early metabolite profiling studies but is now a rapidly expanding area of scientific research in its own right. Metabolomics (or metabonomics) has been labeled one of the new "omics", joining genomics, transcriptomics, and proteomics as a science employed toward the understanding of global systems biology. Metabolomics is fast becoming one of the platform sciences of the "omics", with the majority of the papers in this field having been published only in the last two years. In this review metabolomic methodologies are discussed briefly followed by a more detailed review of the use of metabolomics in integrated applications where metabolomics information has been combined with other "omic" data sets (proteomics, transcriptomics) to enable greater understanding of a biological system. The potential of metabolomics for natural product drug discovery and functional food analysis, primarily as incorporated into broader "omic" data sets, is discussed.

An endophytic fungus from Nothapodytes foetida that produces camptothecin.

Abstract: A fungal endophytic isolate, camptothecin, has been isolated from the inner bark of the plant Nothapodytes foetida from the Western coast of India. The fungus, which belongs to the family Phycomycetes, produced the anticancer drug lead compound camptothecin (1) when grown in a synthetic liquid medium (Sabouraud broth) under shake flask and bench scale fermentation conditions. Compound 1 was identified by means of chromatographic and spectroscopic methods. It was also compared with an authentic example for its biological activity against a number of human cancer cell lines. Isolation of an organism producing 1 and its fermentation may, in the future, provide an easily accessible source for the production of this anticancer drug precursor molecule.

Microbial genomics as a guide to drug discovery and structural elucidation: ECO-02301, a novel antifungal agent, as an example.

Abstract: Analysis of the genome of Streptomyces aizunensis NRRL B-11277 indicated its potential to produce a compound of novel and highly predictable structure. The structure was predicted with sufficient accuracy to allow straightforward detection of the specific metabolite in HPLC profiles of fermentation extracts and hence to guide the isolation. The spectroscopic work was reduced to a confirmation of structure rather than a first principle determination. The compound, ECO-02301 (1), demonstrated potent antifungal activity. This work exemplifies not only the discovery of novel antibiotics from well-characterized organisms but also the utility of genomics as a further tool, complementary to spectroscopy, to enable rapid determination of complex structures.

Isolation of an antiviral polysaccharide, nostoflan, from a terrestrial cyanobacterium, Nostoc flagelliforme.

Abstract: A novel acidic polysaccharide, nostoflan, was isolated from a terrestrial cyanobacterium, Nostoc flagelliforme. Nostoflan exhibited a potent anti-herpes simplex virus type 1 (HSV-1) activity with a selectivity index (50% cytotoxic concentration/50% inhibitory concentration against viral replication) of 13,000. Sugar composition and methylation analyses revealed that it was mainly composed of -->4)-D-Glcp-(1-->, -->6,4)-D-Glcp-(1-->, -->4)-D-Galp-(1-->, -->4)-D-Xylp-(1-->, D-GlcAp-(1-->, D-Manp-(1--> with a ratio of ca. 1:1:1:1:0.8:0.2. Two pyridylaminated oligosaccharides were prepared by partial acid hydrolysis and pyridylamination. On the basis of MALDI-TOF-MS and NMR analyses, they were found to be beta-D-Glcp-(1-->4)-D-Xyl-PA and beta-D-GlcAp-(1-->6)-beta-D-Glcp-(1-->4)-D-Gal-PA. From these results, nostoflan might be mainly composed of the following two types of sugar sequence: -->4)-beta-D-Glcp-(1-->4)-D-Xylp-(1--> and -->4)-[beta-D-GlcAp-(1-->6)-]-beta-D-Glcp-(1-->4)-D-Galp-(1-->. Besides anti-HSV-1 activity, nostoflan showed potent antiviral activities against HSV-2, human cytomegalovirus, and influenza A virus, but no activity against adenovirus and coxsackie virus was observed. Therefore, nostoflan has a broad antiviral spectrum against enveloped viruses whose cellular receptors are carbohydrates. Furthermore, nostoflan showed no antithrombin activity, unlike sulfated polysaccharides.

Chemical Constituents of the Fruits of Morinda citrifolia (Noni) and Their Antioxidant Activity

Abstract: Purification of a n-BuOH-soluble partition of the MeOH extract of Morinda citrifolia (Noni) fruits led to the isolation of two new iridoid glucosides, 6alpha-hydroxyadoxoside (1) and 6beta,7beta-epoxy-8-epi-splendoside (2), as well as 17 known compounds, americanin A (3), narcissoside (4), asperuloside, asperulosidic acid, borreriagenin, citrifolinin B epimer a, citrifolinin B epimer b, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, d-glucose, d-mannitol, methyl alpha-d-fructofuranoside, methyl beta-d-fructofuranoside, nicotifloroside, and beta-sitosterol 3-O-beta-d-glucopyranoside. The structures of the new compounds were determined by spectroscopic data interpretation. Compound 4, borreriagenin, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, methyl alpha-d-fructofuranoside, and methyl beta-d-fructofuranoside were isolated for the first time from M. citrifolia. The antioxidant activity was evaluated for all isolates in terms of both DPPH and ONOO(-) bioassays. The neolignan, americanin A (3), was found to be a potent antioxidant in these assays.

Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients

Abstract: The cardiac glycosides digitoxin (1) and digoxin (3) have been used in cardiac diseases for many years. During this time several reports have suggested the possible use of digitalis in medical oncology. Several analogues of digitoxin (1) were evaluated for growth inhibition activity in three human cancer cell lines; this study showed that digitoxin (1) was the most active compound and revealed some structural features that may play a role in the growth inhibition activity of these drugs. The IC50 values for 1 (3-33 nM) were within or below the concentration range seen in the plasma of patients with cardiac disease receiving this glycoside (20-33 nM). A renal adenocarcinoma cancer cell line (TK-10) was hypersensitive to this drug, and digitoxin toxicity on these cells was mediated by apoptosis. In vitro experiments showed that 1 at 30 nM induced levels of DNA-topoisomerase II cleavable complexes similar to etoposide, a topoisomerase II poison widely used in cancer chemotherapy. Using the individual cell assay TARDIS, cells exposed to 1 for 30 min showed low but statistically significant levels of DNA-topoisomerase II cleavable complexes; however these complexes disappeared after 24 h exposure.

Cytotoxic bisindole alkaloids from a marine sponge Spongosorites sp

Abstract: Three new bisindole alkaloids of the hamacanthin class (1−3) and one new bisindole alkaloid of the topsentin class (6) were isolated along with known bisindole alkaloids (4, 5, 7−11) from the MeOH extract of a marine sponge Spongosorites sp. by bioactivity-guided fractionation. The planar structures were established on the basis of NMR, MS, and IR spectroscopic analyses. Configurations of compounds 1−4 were derived from 1H NMR data and optical rotation. Compounds 1, 4, 5, and 11 showed moderate to significant cytotoxicity against five human tumor cell lines, and compounds 1−5 showed weak antibacterial activity against clinically isolated methicillin-resistant strains.

Antibiotic terpenoid chloro-dihydroquinones from a new marine actinomycete.

Abstract: As part of our continuing interest in exploring the chemistry of actinomycete bacteria uniquely adapted for survival in ocean sediments, we encountered several new strains, which by 16S rDNA sequence-based phylogenetic analysis were recognized as members of a new genus (tentatively called MAR4) within the family Streptomycetaceae. We report here the isolation and structure elucidation of three new chlorinated dihydroquinones (1-3) and one previously reported analogue, 4, from our strain CNQ-525, isolated from ocean sediments collected at a depth of 152 m near La Jolla, California. The compounds formally possess new carbon skeletons, but are related to several previously reported metabolites of the napyradiomycin class. The structures of the new molecules, which possess significant antibiotic properties and cancer cell cytotoxicities, were assigned by comprehensive spectral measurements and by comparison with NMR and other spectral data from the antibiotic A80915C (5), the full stereostructure of which was recently assigned by X-ray diffraction methods.

Exploring the chemistry of uncultivated bacterial symbionts: Antitumor polyketides of the pederin family

Abstract: Symbiotic bacteria have long been proposed as being responsible for the production of numerous natural products isolated from invertebrate animals. However, systematic studies of invertebrate-symbiont associations are usually associated with serious technical challenges, such as the general resistance of symbionts to culturing attempts and the complexity of many microbial consortia. Herein an overview is provided on the culture-independent, metagenomic strategies recently employed by our group to contribute to a better understanding of natural product symbiosis. Using terrestrial Paederus spp. beetles and the marine sponge Theonella swinhoei as model animals, the putative genes responsible for the production of pederin-type antitumor polyketides have been isolated. In Paederus fuscipes, which uses pederin for chemical defense, these genes belong to an as-yet unculturable symbiont closely related to Pseudomonas aeruginosa. To study the extremely complex association of T. swinhoei and its multispecies bacterial consortium, we used a phylogenetic approach that allowed the isolation of onnamide/theopederin polyketide synthase genes from an uncultured sponge symbiont. Analysis of the biosynthesis genes provided unexpected insights into a possible evolution of pederin-type pathways. Besides revealing new facets of invertebrate chemical ecology, these first gene clusters from uncultivated symbiotic producers suggest possible biotechnological strategies to solve the supply problem associated with the development of most marine drug candidates.

Neoglycorandomization and chemoenzymatic glycorandomization: two complementary tools for natural product diversification.

Abstract: In an effort to explore the contribution of the sugar constituents of pharmaceutically relevant glycosylated natural products, chemists have developed glycosylation methods that are amenable to the generation of libraries of analogues with a broad array of glycosidic attachments. Recently, two complementary glycorandomization strategies have been described, namely, neoglycorandomization, a chemical approach based on a one-step sugar ligation reaction that does not require any prior sugar protection or activation, and chemoenzymatic glycorandomization, a biocatalytic approach that relies on the substrate promiscuity of enzymes to activate and attach sugars to natural products. Since both methods require reducing sugars, this review first highlights recent advances in monosaccharide generation and then follows with an overview of recent progress in the development of neoglycorandomization and chemoenzymatic glycorandomization.

A new polyether ladder compound produced by the dinoflagellate Karenia brevis.

Abstract: A new ladder-frame polyether compound containing five fused ether rings was isolated from laboratory cultures of the marine dinoflagellate Karenia brevis. This compound, named brevenal, and its dimethyl acetal derivative both competitively displace brevetoxin from its binding site in rat brain synaptosomes. Significantly, these compounds are also nontoxic to fish and antagonize the toxic effects of brevetoxins in fish. The structure and biological activity of brevenal, as well as the dimethyl acetal derivative, are described in this paper.

Bioactive Benzophenones from Garcinia xanthochymus Fruits

Abstract: A MeOH extract of Garcinia xanthochymus fruits was subjected to activity-guided fractionation, yielding two new benzophenones, guttiferone H (1) and gambogenone (2). Compound 1 contains a seven-membered ring attached to the bicyclo[3.3.1]nonane system at positions 7 and 8 and displayed cytotoxicity in the SW-480 colon cancer cell line (IC(50) = 12 microM). Compound 2 has a novel benzophenone bicyclo[3.3.2]decane system and displayed cytotoxicity in the SW-480 colon cancer cell line (IC(50) = 188 microM). Both 1 and 2 induced apoptosis in SW-480 colon cancer cells and displayed antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (IC(50) = 64 and 38.7 microM, respectively). The structures of 1 and 2 were established by 1D and 2D NMR data analysis. Eleven known compounds, aristophenone A, alloathyriol, amentoflavone, 3,8' '-biapigenin, cycloxanthochymol, (+/-)-fukugetin, (+/-)-fukugiside, guttiferone E, isoxanthochymol, (+/-)-volkensiflavone, and xanthochymol, were also obtained. The 11 known compounds were also tested against SW-480 colon cancer cells and in the DPPH assay.

Biological chemistry of naturally occurring thiols of microbial and marine origin.

Abstract: The presence of thiols in living systems is critical for the maintenance of cellular redox potentials and protein thiol-disulfide ratios, as well as for the protection of cells from reactive oxygen species. In addition to the well-studied tripeptide glutathione (γ-Glu-Cys-Gly), a number of compounds have been identified that contribute to these essential cellular roles. This review provides a survey of the chemistry and biochemistry of several critically important and naturally occurring intracellular thiols such as coenzyme M, trypanothione, mycothiol, ergothioneine, and the ovothiols. Coenzyme M is a key thiol required for methane production in methogenic bacteria. Trypanothione and mycothiol are very important to the biochemistry of a number of human pathogens, and the enzymes utilizing these thiols have been recognized as important novel drug targets. Ergothioneine, although synthesized by fungi and the Actinomycetales bacteria, is present at significant physiological levels in humans and may contribu...

Nitrogen-Containing Compounds from Salvia miltiorrhiza

Abstract: Five new N-containing compounds, neosalvianen (1), salvianen (2), salvianan (3), salviadione (4), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (5), were isolated from Salvia miltiorrhiza. Their structures were mainly established by spectroscopic methods. Neosalvianen (1) and its analogues (6a, 6b) were synthesized for spectroscopic data comparison. Compounds 1, 2, 4, and 6a were evaluated for their cytotoxic activities against selected cancer cell lines. Among these components, salvianen (2) exhibited the most potent cytotoxicity with a CD50 range of 30.4-39.5 microM against HeLa (cervical epitheloid carcinoma), HepG2 (hepatocellular carcinoma), and OVCAR-3 (ovarian adenocarcinoma) cell lines in a dose-dependent manner. The cytotoxicities of the tested compounds were not specific and showed similar activities to the selected cancer cell lines.

Nematicidal epipolysulfanyldioxopiperazines from Gliocladium roseum.

Abstract: 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).

Lajollamycin, a Nitro-tetraene Spiro-β-lactone-γ-lactam Antibiotic from the Marine Actinomycete Streptomyces nodosus

Abstract: A strain of Streptomyces nodosus (NPS007994) isolated from a marine sediment collected in Scripps Canyon, La Jolla, California, was found to produce lajollamycin (1), a nitro-tetraene spiro-β-lactone-γ-lactam antibiotic. The structure was established by complete analysis of spectroscopic data and comparison with known antibiotics oxazolomycin (2), 16-methyloxazolomycin (3), and triedimycin B (4). Lajollamycin (1) showed antimicrobial activity against both drug-sensitive and -resistant Gram-positive bacteria and inhibited the growth of B16-F10 tumor cells in vitro.

Three new triterpenes from Nerium oleander and biological activity of the isolated compounds

Abstract: New ursane-type triterpene 1, oleanane-type triterpene 2, and dammarane-type triterpene 15 were isolated from the leaves of Nerium oleander together with 12 known triterpenes, 3beta-hydroxy-12-ursen-28-oic acid (ursolic acid, 3), 3beta,27-dihydroxy-12-ursen-28-oic acid (4), 3beta,13beta-dihydroxyurs-11-en-28-oic acid (5), 3beta-hydroxyurs-12-en-28-aldehyde (6), 28-norurs-12-en-3beta-ol (7), urs-12-en-3beta-ol (8), urs-12-ene-3beta,28-diol (9), 3beta-hydroxy-12-oleanen-28-oic acid (oleanolic acid, 10), 3beta,27-dihydroxy-12-oleanen-28-oic acid (11), 3beta-hydroxy-20(29)-lupen-28-oic acid (betulinic acid, 12), 20(29)-lupene-3beta,28-diol (betulin, 13), and (20S,24R)-epoxydammarane-3beta,25-diol (14). On the basis of their spectroscopic data, the structures of the new compounds 1, 2, and 15 were established as 3beta,20alpha-dihydroxyurs-21-en-28-oic acid, 3beta,12alpha-dihydroxyoleanan-28,13beta-olide, and (20S,24S)-epoxydammarane-3beta,25-diol, respectively. The anti-inflammatory activity of the seven isolated compounds and methyl esters of ursolic acid and oleanoic acid in vitro was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). The anticancer activity of the 14 isolated compounds, including 1, 2, 15, and methyl esters of ursolic acid and oleanolic acid in vitro was examined on the basis of the cell growth inhibitory activities toward three kinds of human cell lines.

Chinikomycins A and B: Isolation, structure elucidation, and biological activity of novel antibiotics from a marine Streptomyces sp isolate M045

Abstract: In our screening of marine Streptomycetes for bioactive principles, two novel antitumor antibiotics designated as chinikomycins A (2a) and B (2b) were isolated together with manumycin A (1), and their structures were elucidated by a detailed interpretation of their spectra. Chinikomycins A (2a) and B (2b) are chlorine-containing aromatized manumycin derivatives of the type 64-pABA-2 with an unusual para orientation of the side chains. They exhibited antitumor activity against different human cancer cell lines, but were inactive in antiviral, antimicrobial, and phytotoxicity tests.

Glaciapyrroles A, B, and C, Pyrrolosesquiterpenes from a Streptomyces sp. Isolated from an Alaskan Marine Sediment

Abstract: A Streptomyces sp. (NPS008187) isolated from a marine sediment collected in Alaska was found to produce three new pyrrolosesquiterpenes, glyciapyrroles A (1), B (2), and C (3), along with the known diketopiperazines cyclo(leucyl-prolyl) (4), cyclo(isoleucyl-prolyl) (5), and cyclo(phenylalanyl-prolyl) (6). The structures of 1, 2, and 3 were established using spectroscopic methods.

Antiviral Terpenoid Constituents of Ganoderma pfeifferi.

Abstract: Four sterols and 10 triterpenes were isolated from the fruiting bodies of Ganoderma pfeifferi, including the three new triterpenes 3,7,11-trioxo-5alpha-lanosta-8,24-diene-26-al (lucialdehyde D, 1), 5alpha-lanosta-8,24-diene-26-hydroxy-3,7-dione (ganoderone A, 2), and 5alpha-lanosta-8-ene-24,25-epoxy-26-hydroxy-3,7-dione (ganoderone C, 3). The structures of 1-3 were determined on the basis of spectroscopic evidence. Antibacterial, antifungal, and antiviral activity were studied for some of the isolated compounds. Ganoderone A (2), lucialdehyde B (4), and ergosta-7,22-dien-3beta-ol (7) were found to exhibit potent inhibitory activity against herpes simplex virus.

Communesins G and H, new alkaloids from the psychrotolerant fungus Penicillium rivulum.

Abstract: Communesins G (1) and H (2), two new alkaloids, have been isolated from the psychrotolerant, new species Penicillium rivulum Frisvad. The compounds were isolated by high-speed countercurrent chromatography and preparative HPLC using UV-guided fractionation. The structures were determined from 1D and 2D NMR techniques and HRESIMS. In contrast to all other known communesins, 1 and 2 were found inactive in antimicrobial, antiviral, and anticancer assays.

Floratheasaponins A-C, acylated oleanane-type triterpene oligoglycosides with anti-hyperlipidemic activities from flowers of the tea plant (Camellia sinensis).

Abstract: The methanolic extract and its n-butanol-soluble fraction from the flowers of the tea plant (Camellia sinensis) were found to suppress serum triglyceride elevation in olive oil-treated mice. From the n-butanol-soluble fraction, three new acylated oleanane-type triterpene oligoglycosides, floratheasaponins A−C (1−3), were isolated together with several flavonol glycosides and catechins. The structures of 1−3 were elucidated on the basis of chemical and physicochemical evidence as 21-O-angeloyl-22-O-acetyltheasapogenol B 3-O-[β-d-galactopyranosyl(1→2)][β-d-xylopyranosyl(1→2)-α-l-arabinopyranosyl(1→3)]-β-d-glucopyranosiduronic acid, 21,22-di-O-angeloyl-R1-barrigenol 3-O-[β-d-galactopyranosyl(1→2)][β-d-xylopyranosyl(1→2)-α-l-arabinopyranosyl(1→3)]-β-d-glucopyranosiduronic acid, and 21-O-angeloyl-22-O-2-methylbutyryl-R1-barrigenol 3-O-[β-d-galactopyranosyl(1→2)][β-d-xylopyranosyl(1→2)-α-l-arabinopyranosyl(1→3)]-β-d-glucopyranosiduronic acid, respectively. Floratheasaponins (1−3) showed inhibitory effects on se...

Isoneocryptolepine, a synthetic indoloquinoline alkaloid, as an antiplasmodial lead compound.

Abstract: The antiprotozoal activities of three naturally occurring isomeric indoloquinoline alkaloids, i.e., cryptolepine (1), neocryptolepine (2), and isocryptolepine (3), and two dimeric indoloquinoline alkaloids, cryptoquindoline (6) and biscryptolepine (7), originally obtained from the plant Cryptolepis sanguinolenta, were compared with those of a new synthetic indoloquinoline isomer, isoneocryptolepine (4), and a quaternary derivative, N-methyl-isocryptolepinium iodide (5). The latter compounds showed a high antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum strain K1 (IC50 of 0.23 ± 0.04 and 0.017 ± 0.004 μM, respectively), while the cytotoxicity (L6 cells) was 4.32 ± 0.04 and 12.7 ± 2.0 μM, respectively. Isoneocryptolepine (4) was found to act as an inhibitor of β-hematin formation and as a DNA-intercalating agent.

Chromenes from the brown alga Sargassum siliquastrum.

Abstract: Sargachromanols A-P (1-16), sixteen new meroterpenoids of the chromene class, were isolated from the brown alga Sargassum siliquastrum collected from Jaeju Island, Korea. On the basis of the combined results of spectral and chemical analyses, the structures of the polyprenyl portions of these chromanol-containing compounds were determined to be linear triprenyls (1 and 2) and tetraprenyls (3-11), while others were the corresponding rearranged (12-15) and cyclized (16) tetraprenyls, respectively. The new compounds exhibited significant antioxidant activity in the DPPH assay. Compounds 7 and 15 also showed inhibitory activity toward butylcholine esterase.

Natural and Synthetic 2,2-Dimethylpyranocoumarins with Antibacterial Activity

Abstract: A new efficient synthetic approach to the natural coumarins 5-hydroxyseselin (5), 5-methoxyseselin (3), and (±) cis-grandmarin (9) is described as well as the synthesis of some new derivatives in the 5-methoxyseselin series (10−15). The natural coumarins 7-hydroxyalloxanthyletin (6), alloxanthoxyletin (8), and dipetalolactone (7) have also been obtained as secondary products. The type of fusion of the pyrano ring in all cases has been established by 2D NMR spectroscopy. The compounds have been studied for their in vitro antibacterial activity, which has been compared with that of some previously synthesized seselin derivatives. The most active compounds were 3, 7, 8, 11, and 14. Some structure−activity relationships are discussed.

An anthraquinone with potent quinone reductase-inducing activity and other constituents of the fruits of Morinda citrifolia (Noni)

Abstract: Morinda citrifolia, commonly known as noni, has a long history of utilization throughout much of tropical Polynesia and is considered to be the second most important medicinal plant in the Hawaiian Islands. Recently, the use of noni as a dietary supplement in the United States has greatly increased. Bioassay-guided fractionation of a dichloromethane-soluble partition of a MeOH extract of noni fruits has led to the isolation of an extremely potent quinone reductase inducer, 2-methoxy-1,3,6-trihydroxyanthraquinone (1). This new anthraquinone (1) was nearly 40 times more potent than a positive control, l-sulforaphane. Furthermore, compound 1 demonstrated no discernible cytotoxicity at the highest dose tested. In addition to compound 1, 11 known compounds were also isolated and identified in the present investigation. This is the first report of the isolation of anthraquinones from noni fruits.

Nostocarboline: isolation and synthesis of a new cholinesterase inhibitor from Nostoc 78-12A

Abstract: A new quaternary beta-carboline alkaloid, nostocarboline, was isolated from the freshwater cyanobacterium Nostoc 78-12A, and its constitution was assigned by 2D-NMR methods. The structure was proven by its total synthesis starting from norharmane via chlorination at C-6 and methylation at N-2. Nostocarboline was found to be a potent butyrylcholinesterase (BChE) inhibitor, with an IC(50) of 13.2 microM. The related 2-methylnorharmane, which is present in the human brain and might be relevant to Parkinson's disease (PD), was also determined to be a BChE inhibitor (11.2 microM). These inhibitory concentrations are comparable to galanthamine, an approved drug for the treatment of Alzheimer's disease (AD). Nostocarboline can thus be considered as a lead for the development of novel neurochemicals.

Anti-inflammatory activity of verminoside from Kigelia africana and evaluation of cutaneous irritation in cell cultures and reconstituted human epidermis

Abstract: Kigelia africana is a plant used in Africa for anti-inflammatory, anti-microbial, and anti-skin-aging effects. Various papers have reported on the composition and biological activities of its CH2Cl2 extracts and dermal formulations. Chemical analysis of a polar extract of fruit from K. africana indicated the presence of verminoside (1), an iridoid, as a major constituent, and of a series of polyphenols such as verbascoside (2). In vitro assays showed that 1 had significant anti-inflammatory effects, inhibiting both iNOS expression and NO release in the LPS-induced J774.A1 macrophage cell line. Cytotoxicity and cutaneous irritation of the extract and of compounds 1 and 2 were investigated. The crude extract and 1 did not affect cell viability in vitro either in cells grown in monolayers (ML) or in the reconstituted human epidermis (RHE, 3D) model; neither caused release of pro-inflammatory mediators or histomorphological modification of RHE.