Showing papers in "Journal of Natural Products in 2009"
TL;DR: The results offer a caution as to the possibility of using endophytic fungi as alternate sources of plant secondary metabolite production, and further studies have been initiated on the analysis of the upstream metabolic intermediates to understand the steps at which the production of the metabolites in question is constrained.
Abstract: The pentacyclic quinoline alkaloid camptothecin (1) is a potent antineoplastic agent. Two of its analogues, 9-methoxycamptothecin (2) and 10-hydroxycamptothecin (3), exhibit similar potency but do not have the potential therapeutic drawbacks produced by unmodified 1. We have established methodology for the isolation and unequivocal identification and characterization of a novel endophytic fungus isolated from the inner bark of the medicinal plant Camptotheca acuminata, which produced 1-3 in rich mycological medium (Sabouraud dextrose broth), under shake-flask fermentation conditions. The fungus was identified by its morphology and authenticated by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S rDNA region). Camptothecin (1) and its analogues were identified by 1H NMR spectroscopy and LC-HRMS and confirmed by comparison with authentic standards. The production pattern of the metabolites over seven successive subculture generations of this endophyte was studied. A sharp attenuation in the production of 1 and 2 was observed from the first- through to the seventh-generation subculture. Therefore, these results offer a caution as to the possibility of using endophytic fungi as alternate sources of plant secondary metabolite production. Further studies have been initiated on the analysis of the upstream metabolic intermediates to understand the steps at which the production of the metabolites in question is constrained.
346 citations
TL;DR: The vinca alkaloids, the combretastatins, NPI-2358, the halichondrin B analogue eribulin, dolastatin 10, noscapine, hemiasterlin, and rhizoxin are discussed as tubulin polymerization inhibitors, while the taxanes and the epothilones are the major classes of tubulin polymers presented.
Abstract: This review provides an overview of the discovery, structures, and biological activities of anticancer natural products that act by inhibiting or promoting the assembly of tubulin to microtubules The emphasis is on providing recent information on those compounds in clinical use or in advanced clinical trials The vinca alkaloids, the combretastatins, NPI-2358, the halichondrin B analogue eribulin, dolastatin 10, noscapine, hemiasterlin, and rhizoxin are discussed as tubulin polymerization inhibitors, while the taxanes and the epothilones are the major classes of tubulin polymerization promoters presented, with brief treatments of discodermolide, eleutherobin, and laulimalide The challenges and future directions of tubulin-interactive natural products-based drug discovery programs are also discussed briefly
303 citations
TL;DR: This review summarizes the current knowledge on hop bitter acids, including both phytochemical aspects, as well as the biological and pharmacological properties of these compounds.
Abstract: Hop acids, a family of bitter compounds derived from the hop plant (Humulus lupulus), have been reported to exert a wide range of effects, both in vitro and in vivo. They exhibit potential anticancer activity by inhibiting cell proliferation and angiogenesis, by inducing apoptosis, and by increasing the expression of cytochrome P450 detoxification enzymes. Furthermore, hop bitter acids are effective against inflammatory and metabolic disorders, which makes them challenging candidates for the treatment of diabetes mellitus, cardiovascular diseases, and metabolic syndrome. This review summarizes the current knowledge on hop bitter acids, including both phytochemical aspects, as well as the biological and pharmacological properties of these compounds.
227 citations
TL;DR: A Trichoderma harzianum strain, isolated from composted hardwood bark in Western Australia, was found to produce a metabolite with antifungal and plant growth promoting activity, which showed antibiotic activity against Pythium irregulare, Sclerotinia sclerotiorum, and Rhizoctonia solani.
Abstract: A Trichoderma harzianum strain, isolated from composted hardwood bark in Western Australia, was found to produce a metabolite with antifungal and plant growth promoting activity The structure and absolute configuration of the fungal compound, harzianic acid (1), were determined by X-ray diffraction studies Harzianic acid showed antibiotic activity against Pythium irregulare, Sclerotinia sclerotiorum, and Rhizoctonia solani A plant growth promotion effect was observed at low concentrations of 1
184 citations
TL;DR: This review aims to give a comprehensive overview on the current knowledge concerning biological halogenations to investigate the biosynthesis of halogenated natural products and the biotechnological potential of Halogenating enzymes.
Abstract: Halogenated natural products are widely distributed in nature, some of them showing potent biological activities. Incorporation of halogen atoms in drug leads is a common strategy to modify molecules in order to vary their bioactivities and specificities. Chemical halogenation, however, often requires harsh reaction conditions and results in unwanted byproduct formation. It is thus of great interest to investigate the biosynthesis of halogenated natural products and the biotechnological potential of halogenating enzymes. This review aims to give a comprehensive overview on the current knowledge concerning biological halogenations.
183 citations
TL;DR: Two new sesquiterpene coumarins were isolated from a CHCl(3)-soluble extract of Ferula assa-foetida through bioassay-guided fractionation and showed greater potency against influenza A virus than amantadine and exhibited the best potency against HepG2, Hep3B, and MCF-7 cancer cell lines.
Abstract: Two new sesquiterpene coumarins, designated 5'-acetoxy-8'-hydroxyumbelliprenin (1) and 10'R-acetoxy-11'-hydroxyumbelliprenin (2), and a new diterpene, 15-hydroxy-6-en-dehydroabietic acid (3), along with 27 known compounds, were isolated from a CHCl(3)-soluble extract of Ferula assa-foetida through bioassay-guided fractionation. The structures of the new metabolites 1-3 were identified by spectroscopic data interpretation and by the Mosher ester method. Compounds 4 and 6-13 showed greater potency against influenza A virus (H(1)N(1)) (IC(50) 0.26-0.86 microg/mL) than amantadine (IC(50) 0.92 microg/mL), and 11 exhibited the best potency (IC(50) 0.51, 2.6, and 3.4 microg/mL) of these compounds against the HepG2, Hep3B, and MCF-7 cancer cell lines, respectively.
178 citations
TL;DR: Nine new cannabinoids were isolated from a high-potency variety of Cannabis sativa and the known sterol beta-sitosterol-3-O-beta-d-glucopyranosyl-6'-acetate was isolated for the first time from cannabis.
Abstract: Nine new cannabinoids (1-9) were isolated from a high-potency variety of Cannabis sativa. Their structures were identified as (+/-)-4-acetoxycannabichromene (1), (+/-)-3''-hydroxy-Delta((4'',5''))-cannabichromene (2), (-)-7-hydroxycannabichromane (3), (-)-7R-cannabicoumarononic acid A (4), 5-acetyl-4-hydroxycannabigerol (5), 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol (6), 8-hydroxycannabinol (7), 8-hydroxycannabinolic acid A (8), and 2-geranyl-5-hydroxy-3-n-pentyl-1,4-benzoquinone (9) through 1D and 2D NMR spectroscopy, GC-MS, and HRESIMS. The known sterol beta-sitosterol-3-O-beta-d-glucopyranosyl-6'-acetate was isolated for the first time from cannabis. Compounds 6 and 7 displayed significant antibacterial and antifungal activities, respectively, while 5 displayed strong antileishmanial activity.
160 citations
TL;DR: Two new 10-oxo-10H-phenaleno[1,2,3-de]chromene-2-carboxylic acids, xanalteric acids, and 11 known secondary metabolites obtained from extracts of the endophytic fungus Alternaria sp.
Abstract: Two new 10-oxo-10H-phenaleno[1,2,3-de]chromene-2-carboxylic acids, xanalteric acids I (1) and II (2), and 11 known secondary metabolites were obtained from extracts of the endophytic fungus Alternaria sp., isolated from the mangrove plant Sonneratia alba collected in China. The metabolites were confirmed to be of fungal origin, and the structures of the new natural products were unambiguously elucidated on the basis of extensive one- and two-dimensional NMR spectroscopic studies and mass spectrometric analysis. The two new compounds 1 and 2 exhibited weak antibiotic activity against multidrug-resistant Staphylococcus aureus. Altenusin (3) displayed broad antimicrobial activity against several additional multidrug-resistant bacterial and fungal strains.
147 citations
TL;DR: The organic extract of a Schizothrix species from a tropical reef near Piedras Gallinas (Caribbean coast of Panama) showed potent initial antimalarial activity against the W2 chloroquine-resistant strain of Plasmodium falciparum.
Abstract: As part of a continuing program to identify novel treatments for neglected parasitic diseases, the Panama International Cooperative Biodiversity Group (ICBG) program has been investigating the antimalarial potential of secondary metabolites from Panamanian marine cyanobacteria. From over 60 strains of cyanobacteria evaluated in our biological screens, the organic extract of a Schizothrix species from a tropical reef near Piedras Gallinas (Caribbean coast of Panama) showed potent initial antimalarial activity against the W2 chloroquine-resistant strain of Plasmodium falciparum. Bioassay-guided fractionation followed by 2D NMR analysis afforded the planar structure of a new and highly functionalized linear peptide, gallinamide A. Subsequent degradation and derivatization methods were used to determine the absolute configuration at most stereogenic centers in this unusual new metabolite.
144 citations
TL;DR: An Australian marine-derived isolate of Aspergillus versicolor yielded the known fungal metabolites sterigmatocystin, violACEol I, violaceol II, diorcinol, (-)-cyclopenol, and viridicatol, along with a new alkaloid, cottoquinazoline A, and two new cyclopentapeptides, cotteslosins A (2) and B (3).
Abstract: An Australian marine-derived isolate of Aspergillus versicolor (MST-MF495) yielded the known fungal metabolites sterigmatocystin, violaceol I, violaceol II, diorcinol, (−)-cyclopenol, and viridicatol, along with a new alkaloid, cottoquinazoline A (1), and two new cyclopentapeptides, cotteslosins A (2) and B (3). Structures for 1−3 and the known compounds were determined by spectroscopic analysis. The absolute configurations of 1−3 were addressed by chemical degradation and application of the C3 Marfey’s method. The use of “cellophane raft” high-nutrient media as a device for up-regulating secondary metabolite diversity in marine-derived fungi is discussed. The antibacterial properties displayed by A. versicolor (MST-MF495) were attributed to the phenols violaceol I, violaceol II, and diorcinol, while cotteslosins 2 and 3 were identified as weak cytotoxic agents.
139 citations
TL;DR: The 3-hydroxy-3-methylglutaryl neohesperidosides of hesperetin and naringenin were isolated and detected from the fruits of bergamot and the structures were determined by spectroscopic and chemical methods.
Abstract: The 3-hydroxy-3-methylglutaryl neohesperidosides of hesperetin (brutieridin, 1) and naringenin (melitidin, 2) were isolated and detected from the fruits of bergamot (Citrus bergamia). The structures of these compounds were determined by spectroscopic and chemical methods.
TL;DR: The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium, and extracts of the fungus exhibited considerable cytotoxicity when tested in vitro against L5178Y cells.
Abstract: The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded five new secondary metabolites, alterporriol G (4) and its atropisomer alterporriol H (5), altersolanol K (11), altersolanol L (12), stemphypyrone (13), and the known compounds 6-O-methylalaternin (1), macrosporin (2), altersolanol A (3), alterporriol E (6), alterporriol D (7), alterporriol A (8), alterporriol B (9), and altersolanol J (10). The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H (4/5) exhibited considerable cytotoxicity against L5178Y cells with an EC(50) value of 2.7 microg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for kinase inhibitory activity in an assay involving 24 different kinases. Compounds 1, 2, 3, and the mixture of 4 and 5 were the most potent inhibitors, displaying EC(50) values between 0.64 and 1.4 microg/mL toward individual kinases.
TL;DR: Five new antibacterial ambiguine K-O isonitriles and eight previously described indole alkaloids were isolated from the cultured cyanobacterium Fischerella ambigua by bioassay-guided fractionation and showed the most potent activity against M. tuberculosis and Bacillus anthracis.
Abstract: Five new antibacterial ambiguine K−O isonitriles (1−5) and eight previously described indole alkaloids were isolated from the cultured cyanobacterium Fischerella ambigua (UTEX 1903) by bioassay-guided fractionation. The planar structures of the new compounds were determined by spectroscopic analysis including MS and 1D and 2D NMR. X-ray crystallography was used to determine the absolute stereoconfiguration of ambiguine K isonitrile. The isolates were evaluated for their antibacterial activities against a set of bacterial targets, including Mycobacterium tuberculosis and Bacillus anthracis. Ambiguine K and M isonitriles showed the most potent activity against M. tuberculosis, with MIC values of 6.6 and 7.5 μM, respectively. Ambiguine A isonitrile showed the most potent activity against B. anthracis, with a MIC of 1.0 μM.
TL;DR: Quercetin (1) is known to have both antioxidant and antinociceptive effects as discussed by the authors, however, the mechanism involved in its antineuropathic effect is not fully elucidated.
Abstract: Quercetin (1) is known to have both antioxidant and antinociceptive effects. However, the mechanism involved in its antinociceptive effect is not fully elucidated. Cytokines and reactive oxygen spe...
TL;DR: Six new ambuic acid derivatives and a new torreyanic acid analogue have been isolated from the crude extract of endophytic fungus Pestalotiopsis sp.
Abstract: Six new ambuic acid (1) derivatives (2−7) and a new torreyanic acid analogue (8) have been isolated from the crude extract of endophytic fungus Pestalotiopsis sp. inhabiting the lichen Clavaroids sp. The structures of these compounds were elucidated primarily by NMR and MS methods, and their absolute configurations were assigned by application of the CD excitation chirality method. Compounds 1 and 2 displayed antimicrobial activity against the Gram-positive bacterium Staphylococcus aureus.
TL;DR: A single specimen of Hexabranchus sanguineus, a nudibranch from the Indo-Pacific that is known to sequester kabiramides B and C and other trisoxazole macrolides, yielded new kabiral analogues, 9-desmethylkbiramide B and 33-methyltetrahydrohalichondramide, and two new unexpected thiazole-containing cyclic peptides in submicromolar amounts.
Abstract: A single specimen of Hexabranchus sanguineus, a nudibranch from the Indo-Pacific that is known to sequester kabiramides B and C and other trisoxazole macrolides, yielded new kabiramide analogues, 9-desmethylkbiramide B and 33-methyltetrahydrohalichondramide, and two new unexpected thiazole-containing cyclic peptides in submicromolar amounts. The structures of these cyclic peptides were determined by analyses of 1D and 2D NMR spectra recorded with a state-of-the-art 1 mm 1H NMR high-temperature superconducting microcryoprobe, together with mass spectra. In addition to two proline residues, each peptide contains a thiazole- or oxazole-modified amino acid residue, together with conventional amino acid residues. All of the amino acid residues were l, as determined by Marfey’s analysis of the acid hydrolysates of the peptides. This is the first report of cyclic thiazole peptides from H. sanguineus. Since thiazole-oxazole-modified peptides are typically associated with cyanobacteria and tunicates, the finding m...
TL;DR: Six new chromones, named pestalotiopsones A-F (1-6), and the known derivative 7-hydroxy-2-(2-Hydroxypropyl)-5-methylchromone (7) were obtained from the mycelia and culture filtrate of the mangrove endophytic fungus Pestalotiopsis sp.
Abstract: Six new chromones, named pestalotiopsones A-F (1-6), and the known derivative 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (7) were obtained from the mycelia and culture filtrate of the mangrove endophytic fungus Pestalotiopsis sp., which was isolated from leaves of the Chinese Mangrove plant Rhizophora mucronata. Their structures were elucidated on the basis of spectroscopic data. Pestalotiopsones A-F are chromones having both an alkyl side chain substituted at C-2 and a free or substituted carboxyl group at C-5. Compound 6 exhibited moderate cytotoxicity against the murine cancer cell line L5178Y, whereas the other investigated compounds proved to be inactive.
TL;DR: The nutrient conditions present in abandoned coal mine drainages create an extreme environment where defensive and offensive microbial interactions could be critical for survival and fitness.
Abstract: The nutrient conditions present in abandoned coal mine drainages create an extreme environment where defensive and offensive microbial interactions could be critical for survival and fitness. Coculture of a mine drainage-derived Sphingomonas bacterial strain, KMK-001, and a mine drainage-derived Aspergillus fumigatus fungal strain, KMC-901, resulted in isolation of a new diketopiperazine disulfide, glionitrin A (1). Compound 1 was not detected in monoculture broths of KMK-001 or KMC-901. The structure of 1, a (3S,10aS) diketopiperazine disulfide containing a nitro aromatic ring, was based on analysis of MS, NMR, and circular dichroism spectra and confirmed by X-ray crystal data. Glionitrin A displayed significant antibiotic activity against a series of microbes including methicillin-resistant Staphylococcus aureus. An in vitro MTT cytotoxicity assay revealed that 1 had potent submicromolar cytotoxic activity against four human cancer cell lines: HCT-116, A549, AGS, and DU145. The results provide further evidence that microbial coculture can produce novel biologically relevant molecules.
TL;DR: It was revealed that the hyp-1 gene was absent in T. subthermophila, indicating that the biosynthetic pathway in the endophytic fungus might be different and/or governed by a different molecular mechanism than the host plant or host cell suspension cultures.
Abstract: The possible microbial mechanism of hypericin (1) and emodin (2) biosynthesis was studied in axenic submerged culture conditions in the endophytic fungus Thielavia subthermophila, isolated from Hypericum perforatum. The growth and secondary metabolite production of the endophyte remained independent of the illumination conditions. This production remained unaltered on spiking the medium with 3 or 5 mM 2, although the biomass accumulation was reduced. Neither emodin anthrone (3) nor protohypericin (4) could be detected at any stage of fermentation, irrespective of either spiking or illumination conditions. The endophytic metabolites exhibited photodynamic cytotoxicity against the human acute monocytic leukemia cell line (THP-1), at 92.7 vs 4.9%, and 91.1 vs 1.0% viability by resazurin and ATPlite assays, in light and in the dark, respectively. In trying to ascertain the presence/expression of the candidate hyp-1 gene in the endophyte, it was revealed that the hyp-1 gene was absent in T. subthermophila, ind...
TL;DR: It is found that luteolin and quercetin are competitive inhibitors and that silibinin is a mixed-type inhibitor of the enzyme in vitro, and, unlike allopurinol, the inhibition is not time-dependent.
Abstract: Xanthine oxidoreductase (XOR) is a molybdenum-containing enzyme that under physiological conditions catalyzes the final two steps in purine catabolism, ultimately generating uric acid for excretion. Here we have investigated four naturally occurring compounds that have been reported to be inhibitors of XOR in order to examine the nature of their inhibition utilizing in vitro steady-state kinetic studies. We find that luteolin and quercetin are competitive inhibitors and that silibinin is a mixed-type inhibitor of the enzyme in vitro, and, unlike allopurinol, the inhibition is not time-dependent. These three natural products also decrease the production of superoxide by the enzyme. In contrast, and contrary to previous reports in the literature based on in vivo and other nonmechanistic studies, we find that curcumin did not inhibit the activity of purified XO nor its superoxide production in vitro.
TL;DR: Three new cyclohexadepsipeptides, arenamides A-C (1-3), were isolated from the fermentation broth of a marine bacterial strain identified as Salinispora arenicola, and the effects of these compounds on chemoprevention and anti-inflammatory characteristics are suggested.
Abstract: Three new cyclohexadepsipeptides, arenamides A-C (1-3), were isolated from the fermentation broth of a marine bacterial strain identified as Salinispora arenicola. The planar structures of these compounds were assigned by detailed interpretation of NMR and MS/MS spectroscopic data. The absolute configurations of the amino acids, and those of the chiral centers on the side chain, were established by application of the Marfey and modified Mosher methods. The effect of arenamides A and B on NFkappaB activity was studied with stably transfected 293/NFkappaB-Luc human embryonic kidney cells induced by treatment with tumor necrosis factor (TNF). Arenamides A (1) and B (2) blocked TNF-induced activation in a dose- and time-dependent manner with IC(50) values of 3.7 and 1.7 microM, respectively. In addition, the compounds inhibited nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production with lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Moderate cytotoxicity was observed with the human colon carcinoma cell line HCT-116, but no cytotoxic effect was noted with cultured RAW cells. Taken together, these data suggest that the chemoprevention and anti-inflammatory characteristics of arenamides A and B warrant further investigation.
TL;DR: Thirteen new acylated iridoids, jatamanvaltrates A-M (1-13), together with nine known valepotriates (14-22), were isolated from the whole plants of Valeriana jatamansi and tested for their cytotoxicity against lung adenocarcinoma, metastatic prostate cancer, colon cancer, and hepatoma cell lines.
Abstract: Thirteen new acylated iridoids, jatamanvaltrates A-M (1-13), together with nine known valepotriates (14-22), were isolated from the whole plants of Valeriana jatamansi (syn. Valeriana wallichii). The structures of these new compounds were assigned by detailed interpretation of spectroscopic data. Jatamanvaltrates D (4) and H (9) are the first examples of naturally occurring valepotriates containing an o-hydroxybenzoyloxy moiety at C-10. All isolated compounds were tested for their cytotoxicity against lung adenocarcinoma (A549), metastatic prostate cancer (PC-3M), colon cancer (HCT-8), and hepatoma (Bel7402) cell lines.
TL;DR: Three new compounds, magnolianone, erythro-honokitriol, and threo-honkitriol are identified and studied for anti-inflammatory and antioxidative activities in Magnolia officinalis.
Abstract: Three new compounds, magnolianone (1), erythro-honokitriol (2), and threo-honokitriol (3), together with 14 known compounds, magnaldehyde (4), magnatriol B (5), randaiol (6), obovatol (7), magnolignan B (8a and 8b), magnolol, honokiol (9), p-hydroxylbenzaldehyde, coniferaldehyde, coniferol alcohol, syringaldehyde, syringaresinol, and acteoside, were isolated from the MeOH-soluble part of a water extract of the stem bark of Magnolia officinalis. Among these compounds, 2-8b were studied for anti-inflammatory and antioxidative activities. Compound 7 displayed more potent antioxidative potential than 9. Compounds 4-7 effectively inhibited LPS-induced NO production, whereas 5 and 6 were more potent than 9.
TL;DR: It is demonstrated that cardiac glycosides may exhibit significant activity against colorectal cancer cell lines, by mechanisms disparate from currently used anticancer drugs, but at concentrations generally considered not achievable in patient plasma.
Abstract: Cardiac glycosides have been reported to exhibit cytotoxic activity against several different cancer types, but studies against colorectal cancer are lacking. In a screening procedure aimed at identifying natural products with activity against colon cancer, several cardiac glycosides were shown to be of interest, and five of these were further evaluated in different colorectal cancer cell lines and primary cells from patients. Convallatoxin (1), oleandrin (4), and proscillaridin A (5) were identified as the most potent compounds (submicromolar IC50 values), and digitoxin (2) and digoxin (3), which are used in cardiac disease, exhibited somewhat lower activity (IC50 values 0.27-4.1 microM). Selected cardiac glycosides were tested in combination with four clinically relevant cytotoxic drugs (5-fluorouracil, oxaliplatin, cisplatin, irinotecan). The combination of 2 and oxaliplatin exhibited synergism including the otherwise highly drug-resistant HT29 cell line. A ChemGPS-NP application comparing modes of action of anticancer drugs identified cardiac glycosides as a separate cluster. These findings demonstrate that such substances may exhibit significant activity against colorectal cancer cell lines, by mechanisms disparate from currently used anticancer drugs, but at concentrations generally considered not achievable in patient plasma.
TL;DR: The selected compounds from the cell-based reporter assay were found to inhibit hypoxia-induced HIF-1alpha accumulation in a dose-dependent manner in human hepatocelluar carcinoma cell-line Hep3B cells and were also active against hypoxIA-induced vascular endothelial growth factor (VEGF) secretion in Hep3 B cells.
Abstract: Hypoxia-inducible factor-1 (HIF-1) is the central mediator of cellular responses to low oxygen concentrations and vital to many aspects of cancer biology. Bioassay-guided fractionation of the chloroform-soluble extracts of Morus species using a hypoxia response element (HRE)-dependent reporter assay led to identification of six benzofurans (1-6) and two chalcone-derived Diels-Alder adducts (7, 8) from Mori Cortex Radicis and three prenylated benzofurans (9-11) and four chalcone-derived Diels-Alder adducts (12-15) from Morus bombycis. The structure of the new 2-arylbenzofuran-type compound, moracin Q (3), was elucidated by spectroscopic methods, and the absolute configuration of 2 was determined for the first time. The selected compounds (1-3, 5, 7, 9, 10, and 12) from the cell-based reporter assay were found to inhibit hypoxia-induced HIF-1alpha accumulation in a dose-dependent manner in human hepatocelluar carcinoma cell-line Hep3B cells. Furthermore, these compounds were also active against hypoxia-induced vascular endothelial growth factor (VEGF) secretion in Hep3B cells.
TL;DR: Two new alkaloids, named 9- deacetylfumigaclavine C and 9-deacetoxyfumigAClavineC, along with 12 known compounds, were isolated from the culture of Aspergillus fumigatus and showed selectively potent cytotoxicity against human leukemia cells.
Abstract: Two new alkaloids, named 9-deacetylfumigaclavine C (1) and 9-deacetoxyfumigaclavine C (2), along with 12 known compounds (3−14), were isolated from the culture of Aspergillus fumigatus. The structures of the new compounds were elucidated by comprehensive spectroscopic analyses. Compound 2 showed selectively potent cytotoxicity against human leukemia cells (K562) with an IC50 value of 3.1 μM, which was comparable to that of doxorubicin hydrochloride, a presently prescribed drug for the treatment of leukemia. Furthermore, 14-norpseurotin (4) significantly induced neurite outgrowth of rat pheochromocytoma cells (PC12) at a 10.0 μM concentration.
TL;DR: In contrast to previous work on other viruses, the antiviral activity of 13 was mapped to take place in virus replication phase and the efficacy was also shown to be independent of external guanosine supplementation.
Abstract: This paper describes inhibition of Semliki Forest virus (SFV) replication by synthetic derivatives of naturally occurring triterpenoid betulin (1). Chemical modifications were made to OH groups at C-3 and C-28 and to the C-20-C-29 double bond. A set of heterocyclic betulin derivatives was also assayed. A free or acetylated OH group at C-3 was identified as an important structural contributor for anti-SFV activity, 3,28-di-O-acetylbetulin (4) being the most potent derivative (IC50 value 9.1 microM). Betulinic acid (13), 28-O-tetrahydropyranylbetulin (17), and a triazolidine derivative (41) were also shown to inhibit Sindbis virus, with IC50 values of 0.5, 1.9, and 6.1 microM, respectively. The latter three compounds also had significant synergistic effects against SFV when combined with 3'-amino-3'-deoxyadenosine. In contrast to previous work on other viruses, the antiviral activity of 13 was mapped to take place in virus replication phase. The efficacy was also shown to be independent of external guanosine supplementation.
TL;DR: From Allium stipitatum, three pyridine-N-oxide alkaloids possessing disulfide functional groups were isolated and shown to give complete inhibition of the incorporation of (14)C-labeled acetate into soluble fatty acids, indicating that it is potentially an inhibitor of fatty acid biosynthesis.
Abstract: From Allium stipitatum, three pyridine-N-oxide alkaloids (1-3) possessing disulfide functional groups were isolated. The structures of these natural products were elucidated by spectroscopic means as 2-(methyldithio)pyridine-N-oxide (1), 2-[(methylthiomethyl)dithio]pyridine-N-oxide (2), and 2,2'-dithio-bis-pyridine-N-oxide (3). The proposed structure of 1 was confirmed by synthetic S-methylthiolation of commercial 2-thiopyridine-N-oxide. Compounds 1 and 2 are new natural products, and 3 is reported for the first time from an Allium species. All compounds were evaluated for activity against fast-growing species of Mycobacterium, methicillin-resistant Staphylococcus aureus, and a multidrug-resistant (MDR) variants of S. aureus. Compounds 1 and 2 exhibited minimum inhibitory concentrations (MICs) of 0.5-8 microg/mL against these strains. A small series of analogues of 1 were synthesized in an attempt to optimize antibacterial activity, although the natural product had the most potent in vitro activity. In a whole-cell assay at 30 microg/mL, 1 was shown to give complete inhibition of the incorporation of (14)C-labeled acetate into soluble fatty acids, indicating that it is potentially an inhibitor of fatty acid biosynthesis. In a human cancer cell line antiproliferative assay, 1 and 2 displayed IC(50) values ranging from 0.3 to 1.8 microM with a selectivity index of 2.3 when compared to a human somatic cell line. Compound 1 was evaluated in a microarray analysis that indicated a similar mode of action to menadione and 8-quinolinol by interfering with the thioredoxin system and up-regulating the production of various heat shock proteins. This compound was also assessed in a mouse model for in vivo toxicity.
TL;DR: A very significant joint-protective effect of these ginger samples is document and suggest that nongingerol components are bioactive and can enhance the antiarthritic effects of the more widely studied gingerols.
Abstract: Ginger (Zingiber officinale) supplements are being promoted for arthritis treatment in western societies on the basis of ginger's traditional use as an anti-inflammatory in Chinese and Ayurvedic medicine. However, scientific evidence of ginger's antiarthritic effects is sparse, and its bioactive joint-protective components have not been identified. Therefore, the ability of a well-characterized crude ginger extract to inhibit joint swelling in an animal model of rheumatoid arthritis, streptococcal cell wall-induced arthritis, was compared to that of a fraction containing only gingerols and their derivatives. Both extracts were efficacious in preventing joint inflammation. However, the crude dichloromethane extract, which also contained essential oils and more polar compounds, was more efficacious (when normalized to gingerol content) in preventing both joint inflammation and destruction. In conclusion, these data document a very significant joint-protective effect of these ginger samples and suggest that nongingerol components are bioactive and can enhance the antiarthritic effects of the more widely studied gingerols.
TL;DR: A high intrinsic activity is described that is not linked to the presence of hydroxy groups or aromaticity in the pigment structure, and implies an enhancement of the antiradical activity of betalains.
Abstract: Free radical scavenging compounds play important roles as health-protecting factors. Betalains are natural water-soluble pigments present in most plant families belonging to the order Caryophyllale...