ABSTRACT
Bioassay-guided fractionation of an extract prepared from the fruiting bodies of a Daedalea sp. has led to the isolation of daedalols A-C (1-3). The structures of these new triterpenes were elucidated based on extensive NMR spectroscopic and mass spectrometric measurements. Assignment of the relative configuration of 3 required the preparation of a suitable derivative via a Payne rearrangement. The aspartic protease BACE1, an Alzheimer's drug target, was inhibited by 3 with an IC(50) value of 14.2 µM.
Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Aspartic Acid Endopeptidases/antagonists & inhibitors , Coriolaceae/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Coriolaceae/metabolism , Humans , Models, Molecular , Nuclear Magnetic Resonance, Biomolecular , Protease Inhibitors/chemistry , Protease Inhibitors/isolation & purification , Protease Inhibitors/pharmacology , Triterpenes/isolation & purificationABSTRACT
An extensive study of the secondary metabolites produced by a new Sticta sp. of lichen has led to the isolation of three new compounds containing the 4-amino-3-hydroxy-5-phenylpentanoic acid residue (Ahppa). The structures of stictamides A-C (1-3) were assigned by 2D NMR spectroscopic and chemical methods. Due to extensive epimerization of the Ahppa residue observed after acid hydrolysis, the configuration of this unit was deduced through conversion of 1 to an appropriate derivative and application of our recently developed statine NMR database. Evaluation of stictamide A against a panel of disease-relevant proteases showed that it inhibited MMP12 at 2.3 µM and significantly reduced invasion in the human glioma cell line U87MG. Docking studies suggest that stictamide A inhibits MMP12 by a non-zinc-binding mechanism.
Subject(s)
Amino Acids/chemistry , Matrix Metalloproteinase Inhibitors , Peptides/chemistry , Peptides/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Humans , Matrix Metalloproteinase 12/chemistry , Models, Molecular , Neoplasm Invasiveness , Protein ConformationABSTRACT
We report here the isolation of five new compounds, dictazoles A and B (1 and 2) and dictazolines C-E (5-7). Evidence is presented for the direct conversion of the cyclobutyl analogue 1 to its cyclohexyl constitutional isomer 5 via a vinyl cyclobutane rearrangement.
Subject(s)
Cyclobutanes/chemistry , Cyclohexanes/chemistry , Imidazoles/chemistry , Indole Alkaloids/chemistry , Spiro Compounds/chemistry , Vinyl Compounds/chemistry , Cross-Linking Reagents , Isomerism , Magnetic Resonance Spectroscopy , Molecular Structure , Spectrophotometry, UltravioletABSTRACT
A lipophilic extract of an eastern Caribbean collection of Lyngbya majuscula yielded two new halogenated fatty acid amides, grenadamides B (1) and C (2), and two new depsipeptides, itralamides A (3) and B (4), along with the known compounds hectochlorin and deacetylhectochlorin. The recently reported depsipeptide carriebowmide (5) was also present in the extract and isolated as its sulfone artifact (6). Compounds 1-4 were identified by spectroscopic methods. The configurations of the amino acid residues of 3, 4, and 6 were determined by LC-MS analyses of diastereomeric derivatives of the acid hydrolysates (advanced Marfey's method). Based on the configurational analysis of 6, in direct comparison with authentic carriebowmide (5), a minor structural revision of 5 is proposed. Compounds 1 and 2 displayed marginal activity against the beet armyworm (Spodoptera exigua). Compounds 1-4 and 6 were assessed for general cell toxicity in human embryonic kidney (HEK293) cells. Only itralamide B (4) displayed significant cytotoxicity, showing an IC(50) value of 6 +/- 1 muM.
Subject(s)
Amides , Depsipeptides/isolation & purification , Fatty Acids, Unsaturated/isolation & purification , Hydrocarbons, Halogenated/isolation & purification , Animals , Cyanobacteria/chemistry , Depsipeptides/chemistry , Depsipeptides/pharmacology , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/pharmacology , Female , Grenada , Humans , Hydrocarbons, Halogenated/chemistry , Hydrocarbons, Halogenated/pharmacology , Kidney/cytology , Kidney/drug effects , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Spodoptera/drug effectsABSTRACT
An extensive study of the secondary metabolites produced by the marine sponge Smenospongia cerebriformis has led to the isolation of two new bisspiroimidazolidinone derivatives, dictazolines A (1) and B (2), along with the known soft coral metabolites tubastrindoles A (3) and B (4). The structures were assigned by 2D NMR spectroscopic methods.
Subject(s)
Imidazoles/isolation & purification , Indoles/isolation & purification , Porifera/chemistry , Spiro Compounds/isolation & purification , Animals , Anthozoa/chemistry , Imidazoles/chemistry , Indoles/chemistry , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Spiro Compounds/chemistryABSTRACT
The possibility of using the volatile-producing fungus Muscodor albus for biofumigation against building molds was investigated. Several species of Aspergillus and Penicillium as well as fungi belonging to nine other genera were inhibited or killed in vitro by volatiles produced by potato dextrose agar or rye grain cultures of M. albus. Trichoderma viride was the only fungus that was not inhibited by M. albus volatiles. To test biofumigation as a preventative treatment against fungal colonization of building material, dry pieces of gypsum drywall were fumigated with grain cultures of M. albus in closed boxes. After a simulated water damage and incubation under saturated humidity for 2 weeks, untreated drywall developed natural fungal populations of about 10(5)-10(6) cfu/cm2, while drywall fumigated with M. albus culture (20 g/11 L) had nondetectable fungal populations. To test for curative ability, moist pieces of drywall heavily colonized with Cladosporium cladosporioides, Aspergillus niger, or Stachybotrys chartarum were fumigated for 48 h with grain cultures of M. albus. Cladosporium cladosporioides was eliminated within 48 h, while A. niger and S. chartarum were usually more resistant. However, a longer curative fumigation of 96 h was effective in reducing A. niger or naturally occurring mold populations by about 5 log values. The production of volatile organic compounds from 20 g of rye grain culture in 11 L containers was monitored by solid-phase micro extraction and gas chromatography. Concentrations of isobutyric acid, the most abundant volatile, increased gradually in the headspace until it reached 25 microg/L (m/v) within 96 h. The second and third most abundant compounds, 2-methyl-1-butanol and isobutanol, peaked at about 10 and 5 microg/L (m/v), respectively, within the first 24 h and declined gradually afterwards.
Subject(s)
Antifungal Agents/metabolism , Ascomycota/metabolism , Fumigation/methods , Fungi/drug effects , Manufactured Materials/microbiology , Organic Chemicals/metabolism , Ascomycota/growth & development , Culture Media , Fungi/classification , Fungi/growth & development , Housing , VolatilizationABSTRACT
A new indolo[3,2-b]quinoline alkaloid glycoside, jusbetonin (1), and three known alkaloids, namely, 10H-quindoline (2), 6H-quinindoline (3), and 5H,6H-quinindolin-11-one (4), have been isolated from the leaves of Justicia betonica. The structure of 1 was established on the basis of 1D and 2D NMR ((1)H-(1)H COSY, HMQC, and HMBC) and HRFABMS data. Compound 1 is the first example of a glycosylated indolo[3,2-b]quinoline alkaloid, while compound 4 was isolated for the first time from a natural source.
Subject(s)
Acanthaceae/chemistry , Indole Alkaloids/isolation & purification , Quinolines/isolation & purification , Quinolones/isolation & purification , India , Indole Alkaloids/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Leaves/chemistry , Quinolines/chemistry , Quinolones/chemistryABSTRACT
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.
