Chemometric Characterization of Fruit Juices from Spanish Cultivars According to Their Phenolic Compound Contents: I. Citrus Fruits

The data set composed by phenolic compound profiles of 83 <i>Citrus</i> juices (determined by HPLC-DAD-MS/MS) was evaluated by chemometrics to differentiate them according to <i>Citrus</i> species (sweet orange, tangerine, lemon, and grapefruit). Cluster analysis (CA) and principal component analysis (PCA) showed natural sample grouping among <i>Citrus</i> species and even the <i>Citrus</i> subclass. Most of the information contained in the full data set can be captured if only 15 phenolic compounds (concentration ≥10 mg/L), which can be quantified with fast and accurate methods in real samples, are introduced in the models; a good classification which allows the confirmation of the authenticity of juices is achieved by linear discriminant analysis. Using this reduced data set, fast and routine methods have been developed for predicting the percentage of grapefruit in adulterated sweet orange juices using principal component regression (PCR) and partial least-squares regression (PLS). The PLS model has provided suitable estimation errors

MDN-0171, a new medermycin analogue from <i>Streptomyces albolongus</i> CA-186053

<p>A new medermycin derivative, MDN-0171 (<b>1</b>), and two known structurally related compounds, medermycin (<b>2</b>) and antibiotic G15-F (<b>3</b>) were isolated from the acetone extract of culture broths of the marine-derived <i>Streptomyces albolongus</i> strain CA-186053. Their structures were determined using a combination of spectroscopic techniques, including 1D and 2D NMR and electrospray-time of flight mass spectrometry (ESI-TOF MS). Compounds <b>2</b> and <b>3</b> accounted for the antimicrobial activity (against methicillin-resistant <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>) previously detected in the crude extract of this actinomycete.</p

Primary screening identifies compounds capable of inducing FOXO translocation.

<p>(A) U2fox RELOC cells were treated either with DMSO, 4nM LMB, 10μM of compound LOM 612 or compound LOM 621 for 30 min. representative images are shown. (B) Dose-response relationship of the nuclear–cytoplasmic shuttling of FOXO following LOM 612 treatment. LOM612 induces nuclear translocation in a dose dependent manner. Represented is the percentage of cells with more GFP fluorescence accumulation in nucleus than in cytoplasm. Results represent the mean of three independent experiments.</p

Synthesis of compounds 1a-c (LOM612/621/604).

<p>(a) chlorocarbonylsulphenyl chloride, <i>N</i>, <i>N</i>-dimethylurea or <i>N</i>,<i>N</i>-dibenzylurea, acetonitrile, 2h RT for <b>3a</b>: 84%, <b>3b</b>: 62%; chlorocarbonylsulphenyl chloride, benzamide, toluene, 3h, reflux <b>3c</b>: 70%; (b) 1,4-naftochinone, <b>3a</b>, xilene, 80°C, 3h, 23%; 1,4-naftochinone, <b>3b</b>, xylene, 80°C, 3h, 63%; (C) 1,4-naftochinone, <b>3c</b>, xilene, 8h, reflux, 3h, 38%; d) CAN, CH₃CN: H₂O 9:1, 1h, RT, 89%.</p

Results of bioactivity by genera and screening method (<i>Janus</i> and Duetz systems) obtained against <i>Bacillus subtilis</i>, <i>Staphylococcus aureus</i> MRSA, <i>Aliivibrio fisheri</i> and <i>Vibrio harveyi.</i>

<p>Results of bioactivity by genera and screening method (<i>Janus</i> and Duetz systems) obtained against <i>Bacillus subtilis</i>, <i>Staphylococcus aureus</i> MRSA, <i>Aliivibrio fisheri</i> and <i>Vibrio harveyi.</i></p

LOM612 compromises the viability of human cancer cell lines.

<p>(A) Breast cancer cell line MCF7, melanoma cell line A2058 and the neuroblastoma cell line SH-SY5 were seeded at a concentration of 1× 10⁴ cells/well in 200 μl and treated with compounds LOM612 and LOM621 for 72 hours with eight 2-fold serial dilutions of each compound spanning concentrations from 50μM to 0.39μM. Data is shown as mean ± SEM of three independent experiments. ****<i>P</i><0.0001 by two-way ANOVA (ns, not significant). (B) Human liver cancer cell lines HepG2 and THLE-2 (cell line derived from primary normal liver epithelial cells) were seeded at a concentration of 1× 10⁴ cells/well in 200 μl and treated with 20 different concentrations of LOM612 from 50μM to 95pM. Data is shown as mean ± SEM of three independent experiments. ****<i>P</i><0.0001 by two-way ANOVA.</p

LOM612 specifically induces the nuclear translocation of endogenous FOXO proteins.

<p>(A) Compound LOM612 induces the nuclear translocation of endogenous FOXO3a and FOXO1 protein detected by using a specific antibodies after 30 min of drug exposure. (B) LOM612 does not inhibit the nuclear export. U2OS cells stably expressing nuclear export signal (NES) (Rev-NES-EGFP) reporter were treated with DMSO, LMB, LOM612 and LOM621 for 30 min. (C) LOM612 does not induce nuclear translocation of endogenous nuclear factor (NF)–κB2 protein. Representative images of the compound-treated cells using a Leica SPE confocal imaging system. Cells were seeded automatically at appropriate density in 96-well black-wall clear-bottom tissue culture plates and allowed to attach overnight. Cells were then treated with compounds for 30 min before paraformaldehyde (Rev-NES-EGFP) or methanol (FOXO3a, NFKB2) fixation and DAPI staining.</p

Taxonomic affiliation of the bioactive bacteria isolated from <i>E. discophorus</i>.

<p>Taxonomic affiliation of the bioactive bacteria isolated from <i>E. discophorus</i>.</p

Non-geminal Aliphatic Dihalogenation Pattern in Dichlorinated Diaporthins from <i>Hamigera fusca</i> NRRL 35721

Two new epimeric dihalogenated diaporthins, (9<i>R</i>^<i>*</i>)-8-methyl-9,11-dichlorodiaporthin (<b>2</b>) and (9<i>S</i>^<i>*</i>)-8-methyl-9,11-dichlorodiaporthin (<b>3</b>), have been isolated from the soil fungus <i>Hamigera fusca</i> NRRL 35721 alongside the known regioisomeric isocoumarin 8-methyl-11,11-dichlorodiaporthin (<b>1</b>). Their structures were elucidated by high-resolution mass spectrometry and NMR spectroscopy combined with molecular modeling. Compounds <b>1</b>–<b>3</b> are the first isocoumarins and the first halogenated metabolites ever reported from the <i>Hamigera</i> genus. The new compounds <b>2</b> and <b>3</b> display a non-geminal aliphatic dichlorination pattern unprecedented among known fungal dihalogenated aromatic polyketides. A bifunctional methyltransferase/aliphatic halogenase flavoenzyme is proposed to be involved in the biosynthesis of dichlorinated diaporthins <b>1</b>–<b>3</b>. These metabolites are weakly cytotoxic

Cyclic Colisporifungin and Linear Cavinafungins, Antifungal Lipopeptides Isolated from <i>Colispora cavincola</i>

Colisporifungin (<b>1</b>), a cyclic depsilipopeptide structurally related to the aselacins, and cavinafungins A and B, two linear peptides, were isolated from liquid culture broths of the hitherto unstudied fungus <i>Colispora cavincola</i> using a <i>Candida albicans</i> whole-cell assay as well as a bioassay to detect compounds potentiating the antifungal activity of caspofungin. The structural elucidation, including the absolute configuration of the new molecules, was accomplished using a combination of spectroscopic and chemical techniques, including 1D and 2D NMR, HRMS, and Marfey’s analysis. The cyclic peptide colisporifungin displayed a strong potentiation of the growth inhibitory effect of caspofungin against <i>Aspergillus fumigatus</i> and, to a lesser extent, against <i>Candida albicans</i>. The linear peptides displayed broad-spectrum antifungal activities inhibiting growth of <i>Candida</i> species (MIC values 0.5–4 μg/mL) as well as <i>A. fumigatus</i> with a prominent inhibition of 8 μg/mL