Snake venom phospholipase A(2) inhibitors: Medicinal chemistry and therapeutic potential

Phospholipases A(2) (PLA(2)s) are commonly found in snake venoms from Viperidae, Hydrophidae and Elaphidae families and have been extensively studied due to their pharmacological and physiopathological effects in living organisms. This article reports a review on natural and artificial inhibitors of enzymatic, toxic and pharmacological effects induced by snake venom PLA(2)s. These inhibitors act on PLA(2)S through different mechanisms, most of them still not completely understood, including binding to specific domains, denaturation, modification of specific amino acid residues and others. Several substances have been evaluated regarding their effects against snake venoms and isolated toxins, including plant extracts and compounds from marine animals, mammals and snakes serum plasma, in addition to poly or monoclonal antibodies and several synthetic molecules. Research involving these inhibitors may be useful to understand the mechanism of action of PLA(2)s and their role in envenomations caused by snake bite. Furthermore, the biotechnological potential of PLA(2) inhibitors may provide therapeutic molecular models with antiophidian activity to supplement the conventional serum therapy against these multifunctional enzymes.

Theoretical study of omeprazole behavior: Racemization barrier and decomposition reaction

omeprazole is a substituted benzimidazole which suppresses gastric-acid secretion by means of H+, K+-ATPase inhibition. It is an optically active drug with the sulfur of the sulfoxide being the chiral center. This pro-drug can be easily converted into its respective sulfenamide at low pH. In this work, omeprazole has been studied in relation to racemization barrier and decomposition reaction. Quantum chemistry coupled to PCA chemometric method were used to find all minimum energy structures. Conformational analysis and calculation of racemization barriers were carried out by PM3 semiempirical method (Gaussian 98). The average racemization energy barrier for all minimum energy structures (43.56 kcal mol(-1)) can be related to the velocity constant in Eyring's equation. The enormous half-life time at 100 degrees C (9.04 x 10(4) years) indicates that the process cannot be observed in human time scale. on the other hand, the difference of free energy change (Delta(Delta G) = -266.78 kcal mol(-1)) for the decomposition reaction shows that the process is favorable to the sulfenamide formation. The highly negative Delta(Delta G) obtained for the decomposition reaction shows that this process is extremely exothermic. This result explains why omeprazole decomposes and does not racemize. (C) 2008 Wiley Periodicals, Inc.

On the search for potential anti-Trypanosoma cruzi drugs: Synthesis and biological evaluation of 2-hydroxy-3-methylamino and 1,2,3-triazolic naphthoquinoidal compounds obtained by click chemistry reactions

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Mercury Redox Chemistry in the Negro River Basin, Amazon: The Role of Organic Matter and Solar Light

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Podzolization as a deferralitization process: dynamics and chemistry of ground and surface waters in an Acrisol-Podzol sequence of the upper Amazon Basin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ferroelectric and dielectric behaviour of Bi0.92La0.08FeO3 multiferroic thin films prepared by soft chemistry route

Bi0.92La0.08FeO3 (BLFO) thin films were grown on platine substrates by the soft chemical route. Ferroelectric and dielectric behaviors of BLFO films deposited by spin-coating technique and annealed at 773 K for 2 h in air atmosphere were explained. BLFO thin films obtained presents a rhombohedral structure. The BLFO films present dielectric and ferroelectric behaviors with dielectric permittivity and dielectric loss of approximately 81 and 0.0144 at 1 kHz. The Au/BLFO/Pt capacitor shows a hysteresis loop with remnant polarization of 20.6 mu C/cm(2) and coercive field of 53.88 kV/cm. The polarization switching and the fatigue behavior of the BLFO films were significantly enhanced.

Electrochemical Behavior of a Glassy Carbon Electrode Chemically Modified with Nickel Pentacyanonitrosylferrate in Presence of Sulfur Compounds

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Determination of sulfur compounds in gasoline using mercury film electrode by square wave voltammetry

A sensitive method based on square wave voltammetry is described for the quantitative determination of elemental sulfur, disulfide and mercaptan in gasoline using a mercury film electrode. These sulfur compounds can be quantified by direct dissolution of gasoline in a supporting electrolyte followed by subsequent voltammetric measurement. The supporting electrolyte is 1.4 mol L-1 sodium acetate and No acetic acid in methanol. Chemical and optimum operational conditions for the formation of the mercury film were analyzed in this study. The values obtained were a 4.3 mu m thickness for the mercury film, a 1000 rpm rotation frequency, -0.9 V applied potential and 600 s depositing time. Voltammetric measurements were obtained using square wave voltammetry with detection limits of the 3.0 x 10(-9), 1.6 x 10(-7) and 4.9 x 10(-7) mol L-1 for elemental sulfur, disulfide and mercaptan, respectively. (C) 2007 Elsevier Ltd. All rights reserved.

Natural products from Brazilian biodiversity as a source of new models for medicinal chemistry

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tropical biodiversity: has it been a potential source of secondary metabolites useful for medicinal chemistry?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cinética e mecanismo da reação de auto-oxidação deS(IV) catalisada por íons metálicos de transição

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hydroxymethylnitrofurazone:Dimethyl-beta-cyclodextrin Inclusion Complex: A Physical-Chemistry Characterization

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Gas chromatographic-olfactometric characterization of aroma compounds in two types of cashew apple nectar

Cashew apple nectar is a secondary product from the production of cashew nuts and possesses an exotic tropical aroma. Aroma volatiles in pasteurized and reconstituted (from concentrate) Brazilian cashew apple nectars were determined using GC-MS and split, time-intensity GC-olfactometry (GC-O/GC-FID. Methional, (2)-1,5-octadien-3-one, (2)-2-nonenal, (E,Z)-2,4-decadienal, (E,E)-2,4-decadienal, beta-damascenone, and delta-decalactone were identified for the first time in cashew apple products. These compounds plus butyric acid, ethyl 3-methylbutyrate, 2-methylbutyric acid, acetic acid, benzaldehyde, homofuraneol, (E)-2-nonenal, gamma-dodecalactone, and an unknown were the most intense aroma volatiles. Thirty-six aroma volatiles were detected in the reconstituted sample and 41 in the pasteurized sample. Thirty-four aroma active components were common to both samples. Ethyl 3-methylbutyrate and 2-methylbutyric acid were character impact compounds of cashew apple (warm, fruity, tropical, sweaty). Using GC-pFPD, 2-methyl-3-furanthiol and bis(2-methyl-3-furyl) disulfide were identified for the first time in cashew apple. Both were aroma active (meaty).

APPLICATIONS OF ARTIFICIAL-INTELLIGENCE IN ORGANIC-CHEMISTRY .17. NEW PROGRAMS IN THE SISTEMAT PROJECT

This work describes the new improvements of the SISTEMAT project, one system for structural elucidation mainly in the field of Natural Products Chemistry. Some examples of the resolution of problems using C-13 Nuclear Magnetic Resonance and Mass Spectroscopy are given. Programs to discover new heuristic rules for structure generation are discussed. The data base contains about 10000 C-13 NMR spectra.