A study of the compositional variation of the essential oil of ylang-ylang (Cananga odorata Hook Fil. et Thomson,formagenuina) during flower development

Volatile secondary metabolites from Colombian ylang-ylang flowers were obtained by combined steam distillation - solvent extraction. The samples were analyzed by high resolution gas chromatography with flame ionization, nitrogen/phosphorus, or mass spectrometric detection. The chemical composition of the oils extracted from flowers at different stages of development differed both qualitatively and quantitatively. The generation of total volatile metabolites, light oxygenated compounds in particular, increased markedly during flower maturation. In this work the quality of the ylang-ylang essential oils was studied as a function of flower maturity.     

Nitric oxide photorelease from ruthenium salen complexes in aqueous and organic solutions

The complexes [Ru(salen)(NO)Cl] and [Ru(salen)(NO)(H(2)O)](+) were shown to release the nitrosyl ligand as nitric oxide upon exposure to visible light in organic and aqueous solutions respectively, by means of UV-visible, EPR, and FTIR spectroscopies. The former was prepared by a new synthetic route and had its structure determined by single-crystal X-ray diffraction. A crystal of the dichloromethane solvate is orthorhombic, space group Fdd2 (No. 43) and formula C(16)H(14)ClN(3)O(3)Ru.CH(2)Cl(2), with Z = 16 and cell parameters a = 25.489(4), b = 33.435(4), and c = 9.3716(9) A. The electronic absorption spectra of the complexes were calculated using the INDO/S method. The water-soluble complex is a potential drug for antitumoral phototreatment.     

Calculated structures and relative stabilities of furoxan,some 1,2-dinitrosoethylenes and other isomers

The structures and relative stabilities of furoxan and some of its isomers, e.g., the 1,2-dinitrosoethylenes, have been determined by means of ab initio Hartee–Fock and Møller–Plesset calculations. Geometries were optimized at the HF/3-21G, HF/6-31G* and MP2/6-31G* levels, and subsequently used for computing MP2/6-31G*, MP3/6-31G*, and MP4/6-31G* energies. The results are markedly affected by the inclusion of electronic correlation, which renders three of the isomers unstable. It also emphasizes the importance of a zwitterionic contribution to the structure of furoxan, which promotes ring-opening through a cis 1,2-dinitrosoethylene intermediate/transition state that has an MP4/6-31G*//MP2/6-31G* energy that is 31.6 kcal/mol above furoxan.     

Stereoselective synthesis of hyptolide and 6-epi-hyptolide

The first stereoselective syntheses of the naturally occurring, ,β-unsaturated lactone hyptolide 1 and of its nonnatural epimer at C-6 are described. Ethyl l-lactate was the chiral starting material. Key steps of these syntheses were a Brown's asymmetric allylation, a Carreira's asymmetric ethynylation and a ring closing metathesis.     

Two problematic human polymorphic Alu insertions

Analysis of two previously described polymorphic Alu insertions (Sb19.3 and NBC3) in world-wide human populations generated genotypic frequencies grossly in violation of Hardy-Weinberg equilibrium expectations. GenBank searches at the National Center for Biotechnology Information (NCBI) and sequencing analyses revealed that samples homozygous for the Sb19.3 Alu insertion amplify a band indistinguishable in size to the lack of insertion amplicon, corresponding to a paralogous locus on chromosome 4. This locus displays a very similar sequence (84%) to that flanking the Sb19.3 Alu insertion located at chromosome 19. Moreover, we have determined that NBC3, a different Alu insertion, is not located in the pseudoautosomal region of the Y-chromosome, as previously reported, but in position Yq11.2. Also, the band that mimics the lack of insertion amplicon corresponds to a paralogous locus located at chromosome X with a similarity of 92% to the sequence flanking the NBC3 Alu insertion. Finally, the utilization of newly designed primers avoided amplification from the paralogous loci and allowed a reliable assignation of genotypes for both loci. Unlike previously reported, using our new primers the Y-specific locus NBC3 was found not to be polymorphic in the populations analyzed.     

Poly(ethylene terephthalate) copolymers containing nitroterephthalic units. III. Methanolytic degradation

The methanolytic degradation of poly(ethylene terephthalate) (PET) copolymers containing nitroterephthalic units was investigated. Random poly(ethylene terephthalate‐co‐nitroterephthalate) copolyesters (PETNT) containing 15 and 30 mol % nitrated units were prepared from ethylene glycol and a mixture of dimethyl terephthalate and dimethyl nitroterephthalate. A detailed study of the influence of the nitro group on the methanolytic degradation rate of the nitrated bis(2‐hydroxyethyl) nitroterephthalate (BHENT) model compound in comparison with the nonnitrated bis(2‐hydroxyethyl) terephthalate (BHET) model compound was carried out. The kinetics of the methanolysis of BHENT and BHET were evaluated with high‐performance liquid chromatography and ¹H NMR spectroscopy. BHENT appeared to be much more reactive than BHET. The methanolytic degradation of PET and PETNT copolyesters at 80 °C was followed by changes in the weight and viscosity, gel permeation chromatography, differential scanning calorimetry, scanning electron microscopy, and ¹H and ¹³C NMR spectroscopy. The copolyesters degraded faster than PET, and the degradation increased with the content of nitrated units and occurred preferentially by cleavage of the ester groups placed at the meta position of the nitro group in the nitrated units. For both PET and PETNT copolyesters, an increase in crystallinity accompanied methanolysis. A surface degradation mechanism entailing solubilization of the fragmented polymer and consequent loss of mass was found to operate in the methanolysis of the copolyesters. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2276–2285, 2002     

Synthesis,Leishmanicidal, Trypanocidal,Antiproliferative Assay and Apoptotic Induction of (2-Phenoxypyridin-3-yl)naphthalene-1(2H)-one Derivatives

The coexistence of leishmaniasis, Chagas disease, and neoplasia in endemic areas has been extensively documented. The use of common drugs in the treatment of these pathologies invites us to search for new molecules with these characteristics. In this research, we report 16 synthetic chalcone derivatives that were investigated for leishmanicidal and trypanocidal activities as well as for antiproliferative potential on eight human cancers and two nontumor cell lines. The final compounds 8–23 were obtained using the classical base-catalyzed Claisen–Schmidt condensation. The most potent compounds as parasiticidal were found to be 22 and 23, while compounds 18 and 22 showed the best antiproliferative activity and therapeutic index against CCRF-CEM, K562, A549, and U2OS cancer cell lines and non-toxic VERO, BMDM, MRC-5, and BJ cells. In the case of K562 and the corresponding drug-resistant K562-TAX cell lines, the antiproliferative activity has shown a more significant difference for compound 19 having 10.3 times higher activity against the K562-TAX than K562 cell line. Flow cytometry analysis using K562 and A549 cell lines cultured with compounds 18 and 22 confirmed the induction of apoptosis in treated cells after 24 h. Based on the structural analysis, these chalcones represent new compounds potentially useful for Leishmania, Trypanosoma cruzi, and some cancer treatments.     

Kribbellichelins A and B,Two New Antibiotics from Kribbella sp. CA-293567 with Activity against Several Human Pathogens

Current needs in finding new antibiotics against emerging multidrug-resistant superbugs are pushing the scientific community into coming back to Nature for the discovery of novel active structures. Recently, a survey of halophilic actinomyectes from saline substrates of El Saladar del Margen, in the Cúllar-Baza depression (Granada, Spain), led us to the isolation and identification of 108 strains from the rhizosphere of the endemic plant Limonium majus. Evaluation of the potential of these strains to produce new anti-infective agents against superbug pathogens was performed through fermentation in 10 different culture media using an OSMAC approach and assessment of the antibacterial and antifungal properties of their acetone extracts. The study allowed the isolation of two novel antibiotic compounds, kribbellichelin A (1) and B (2), along with the known metabolites sandramycin (3), coproporphyrin III (4), and kribelloside C (5) from a bioassay-guided fractionation of scaled-up active extracts of the Kribbella sp. CA-293567 strain. The structures of the new molecules were elucidated by ESI-qTOF-MS/MS, 1D and 2D NMR, and Marfey’s analysis for the determination of the absolute configuration of their amino acid residues. Compounds 1–3 and 5 were assayed against a panel of relevant antibiotic-resistant pathogenic strains and evaluated for cytotoxicity versus the human hepatoma cell line HepG2 (ATCC HB-8065). Kribbellichelins A (1) and B (2) showed antimicrobial activity versus Candida albicans ATCC-64124, weak potency against Acinetobacter baumannii MB-5973 and Pseudomonas aeruginosa MB-5919, and an atypical dose-dependent concentration profile against Aspergillus fumigatus ATCC-46645. Sandramycin (3) confirmed previously reported excellent growth inhibition activity against MRSA MB-5393 but also presented clear antifungal activity against C. albicans ATCC-64124 and A. fumigatus ATCC-46645 associated with lower cytotoxicity observed in HepG2, whereas Kribelloside C (5) displayed high antifungal activity only against A. fumigatus ATCC-46645. Herein, we describe the processes followed for the isolation, structure elucidation, and potency evaluation of these two new active compounds against a panel of human pathogens as well as, for the first time, the characterization of the antifungal activities of sandramycin (3).     

Semisynthetic Abietic and Dehydroabietic Acid Derivatives and Triptoquinone Epimers Interfere with LPS-Triggered Activation of Dendritic Cells

Abietic acid (AA), dehydroabietic acid (DHA) and triptoquinones (TQs) are bioactive abietane-type diterpenoids, which are present in many edible vegetables and medicinal herbs with health-promoting properties. Evidence suggests that beneficial effects of diterpenes operate, at least in part, through effects on cells in the immune system. Dendritic cells (DCs) are a key type of leukocyte involved in the initiation and regulation of the immune/inflammatory response and natural or synthetic compounds that modulate DC functions could be potential anti-inflammatory/immunomodulatory agents. Herein, we report the screening of 23 known semisynthetic AA and DHA derivatives, and TQs, synthesized previously by us, in a multi-analyte DC-based assay that detects inhibition of pro-inflammatory cytokine production. Based on the magnitude of the inhibitory effect observed and the number of cytokines inhibited, a variety of activities among compounds were observed, ranging from inactive/weak to very potent inhibitors. Structurally, either alcohol or methyl ester substituents on ring A along with the introduction of aromaticity and oxidation in ring C in the abietane skeleton were found in compounds with higher inhibitory properties. Two DHA derivatives and two TQs exhibited a significant inhibition in all pro-inflammatory cytokines tested and were further investigated. The results confirmed their ability to inhibit, dose dependently, LPS-stimulated expression of the co-stimulatory molecules CD40 and/or CD86 and the production of the pro-inflammatory cytokines IL-1β, IL-6, IL-12 and TNFα. Our results demonstrate that DC maturation process can be targeted by semisynthetic DHA derivatives and TQ epimers and indicate the potential of these compounds as optimizable anti-inflammatory/immunomodulatory agents.     

Microscopical Evaluation of the Effects of High-Pressure Processing on Milk Casein Micelles

The effect of different high-pressure processing (HPP) treatments on casein micelles was analyzed through scanning electron microscopy (SEM) and a particle size distribution analysis. Raw whole and skim milk samples were subjected to HPP treatments at 400, 500 and 600 MPa for Come-Up Times (CUT) up to 15 min at ambient temperature. Three different phenomena were observed in the casein micelles: fragmentation, alterations to shape and agglomeration. The particle size distribution analysis determined that, as pressure and time treatment increased, the three phenomena intensified. First, the size of the casein micelles began to decrease as their fragmentation occurred. Subsequently, the casein micelles lost roundness, and their shape deformed. Finally, in the most intense treatments (higher pressures and/or longer times), the micelles fragments began to agglomerate, which resulted in an increase in their average diameter. Homogenization and defatting had no significant effect on the casein micelles; however, the presence of fat in whole milk samples was bioprotective, as the effects of the three phenomena appeared faster in treated skim milk samples. Through this study, it was concluded that the size and structure of casein micelles are greatly altered during high-pressure treatment. These results provide information that broadens the understanding of the changes induced on casein micelles by high-pressure treatments at room temperature.