SAR analysis of synthetic neolignans and related compounds which are anti-leishmaniasis active compounds using pattern recognition methods

Potentially active new neolignan and analogues against leishmaniasis are proposed. Structure-activity relationship (SAR) techniques were employed. Physicochemical properties such as log P, molecular volume, atomic charge and quantum chemical parameters were calculated for a group of synthetic substances for which the biological activities against leishmaniasis are known. Only about half a dozen out of more than twenty parameters were found to be efficient for the classification of the compounds into active and inactive groups.     

Antioxidant capacity and phenolic content of four Myrtaceae plants of the south of Brazil

Antioxidant compounds can be useful to prevent several degenerative diseases or as preservative in food and toiletries. Species of the Myrtaceae family are able to accumulate phenolic substances and those are closely related to the antioxidant activity due to their capacity to scavenge free radicals, protect against lipid peroxidation and quench reactive oxygen species. These facts prompted us to investigate the antioxidant capacity of the ethanolic extracts of the leaves of four Myrtaceae plants collected of the south of Brazil: Eugenia chlorophylla O. Berg., Eugenia pyriformis Cambess, Myrcia laruotteana Cambess and Myrcia obtecta (Berg) Kiacrsk. The antioxidant potential was performed using the DPPH (a single electron transfer reaction based assay) and ORAC (Oxygen Radical Absorbance Capacity, a hydrogen atom transfer reaction based assay) assays. Moreover, the total soluble phenolic content was also measured using the Folin-Ciocalteu reagent. A preliminary evaluation of the ethanolic extracts of these Myrtaceae plants revealed high levels of phenolic compounds (343.7-429.3 mg GAE) as well as high antioxidant activity according to both methods (1338 a 3785 micromol of TE/g of extract in ORAC and SC50 in the range of 1.70 and 33.7 microg/mL in the DPPH). The highest antioxidant activity obtained by DPPH assay was exhibited by ethanol extract of the leaves of E. pyriformis (1.70 microg/mL), followed by extracts of M. laruotteana (3.38 microg/mL) and M. obtecta (6.66 microg/mL). In comparison with controls, in the DPPH assay, the extract of E. pyriformis was more active than trolox (SC50 = 2.55 microg/mL), while the extracts of M. laruotteana and M. obtecta were more actives than quercetin (SC50 = 7.80 microg/mL). In the ORAC assay, all species also show good antioxidant capacity (>1000 micromol of TE/g). Initial HPLC-UV/DAD and ESI-MS confirmed the presence of phenolic acids constituents in the ethanol extracts. The results indicate the presence of compounds possessing promising antioxidant/free-radical scavenging activity in the analyzed extracts of Myrcia and Eugenia plants of the south of Brazil.     

Histidine-containing host-defence skin peptides of anurans bind Cu2+. An electrospray ionisation mass spectrometry and computational modelling study

Anuran peptides which contain His, including caerin 1.8 (GLFKVLGSVAKHLLPHVVPVIAEKL‐NH₂), caerin 1.2 (GLLGVLGSVAKHVLPHVVPVIAEHL‐NH₂), Ala₁₅ maculatin 1.1 (GLFGVLAKVAAHVVAIEHF‐NH₂), fallaxidin 4.1 (GLLSFLPKVIGHLIHPPS‐OH), riparin 5.1 (IVSYPDDAGEHAHKMG‐NH₂) and signiferin 2.1 (IIGHLIKTALGMLGL‐NH₂), all form MMet²⁺ and (M + Met²⁺‐2H⁺)²⁺ cluster ions (where Met is Cu, Mg and Zn) following electrospray ionisation (ESI) in a Waters QTOF 2 mass spectrometer. Peaks due to Cu(II) complexes are always the most abundant relative to other metal complexes. Information concerning metal²⁺ connectivity in a complex has been obtained (at least in part) using b and y fragmentation data from ESI collision‐induced dissociation tandem mass spectrometry (CID MS/MS). Theoretical calculations, using AMBER version 10, show that MCu²⁺ complexes with the membrane active caerin 1.8, Ala₁₅ maculatin 1.1 and fallaxidin 4.1 are four‐coordinate and approximating square planar, with ligands including His and Lys, together with the carbonyl oxygens of particular backbone amide groups. When binding can occur through two His, or one His and one Lys, the His/Lys ligand structure is the more stable for the studied systems. The three‐dimensional (3D) structures of the complexes are always different from the previously determined structures of the uncomplexed model peptides (using 2D nuclear magnetic resonance (NMR) spectroscopy in membrane‐mimicking solvents like trifluoroethanol/water). Copyright © 2011 John Wiley & Sons, Ltd.     

HPLC-ESI-MS/MS of imidazole alkaloids in Pilocarpus microphyllus

Pilocarpine, an important imidazole alkaloid, is extracted from the leaves of Pilocarpus microphyllus (Rutaceae), known in Brazil as jaborandi and used mainly for the treatment of glaucoma. Jaborandi leaves also contain other imidazole alkaloids, whose pharmacological and physiological properties are unknown, and whose biosynthetic pathways are under investigation. In the present study, a HPLC method coupled with ESI-MS(n) was developed for their qualitative and quantitative analysis. This method permits the chromatographic separation of the imidazole alkaloids found in extracts of jaborandi, as well as the MS/MS analysis of the individual compounds. Thus two samples: leaves of P. microphyllus and a paste that is left over after the industrial extraction of pilocarpine; were compared. The paste was found to contain significant amounts of pilocarpine and other imidazole alkaloids, but had a slightly different alkaloid profile than the leaf extract. The method is suitable for the routine analysis of samples containing these alkaloids, as well as for the separation and identification of known and novel alkaloids from this family, and may be applied to further studies of the biosynthetic pathway of pilocarpine in P. microphyllus.     

Negative ion fragmentations of deprotonated peptides containing post‐translational modifications: diphosphorylated systems containing Ser,Thr and Tyr. A characteristic phosphate/phosphate cyclisation. A joint experimental and theoretical study

[M–H]^? anions from small diphosphopeptides (phosphate groups on Ser, Thr or Tyr) show characteristic peaks corresponding to m/z 177 (H₃P₂O), 159 (HP₂O) and sometimes [(M‐H)^?–H₄P₂O₇]^?. M/z 177 and m/z 159 are major peaks in the spectra of small peptides with 1,2, 1,3, 1,4, 1,5 and 1,6 diphosphate substitution, which means that the decomposing [M–H]^? anions must have flexible structures in order for the two phosphate groups to interact with each other. Peptides where the two phosphate groups are more than six amino acid residues apart have not been studied. Theoretical calculations indicate that m/z 177 is formed in a strongly exothermic reaction involving facile nucleophilic interaction between the two phosphate groups: m/z 159 is formed by loss of water from energised m/z 177. Copyright © 2009 John Wiley & Sons, Ltd.     

Cluster organization in co-sputtered platinum-carbon films as revealed by grazing incidence X-ray scattering

Nanostructured platinum-carbon thin films were prepared by magnetron co-sputtering method for designing efficient catalytic thin films, like fuel cells electrodes. The in-depth morphology of composite films was studied using surface sensitive X-ray techniques (grazing incidence small-angle scattering and reflectivity), consolidated by electron microscopy investigations. This study elucidates the growth mode of co-sputtered platinum-carbon thin film: 2-nm-sized platinum clusters are growing in surrounding simultaneously growing carbon columns (20-nm diameter range). In particular, the platinum cluster growth and distribution in the plane of the substrate surface are driven by surface diffusion and coalescence phenomena. Finally, this anisotropic distribution of platinum clusters correlated to the textured morphology of carbon matrix leads to a catalytic thin film morphology very suitable for electrochemical processes in fuel cell electrodes.