The activity of a metronidazole analogue and its β-cyclodextrin complex against Trypanosoma cruzi

In this study we prepared an inclusion complex between an iodide analogue of metronidazole (MTZ-I) and cyclodextrin (CD) to develop a safer and more effective method of treating Trypanosoma cruzi infections. According to our results, MTZ-I and MTZ-I:β-CD were 10 times more active than MTZ, demonstrating that the presence of an iodine atom on the side chain increased the trypanocidal activity while maintaining its cytotoxicity. The selective index shows that MTZ-I was 10 times more active against T. cruzi than it was against mammalian cells. The modification of MTZ side chains provides a promising avenue for the development of new drugs.

Estudos de QSAR baseados em dados de atividade biológica obtidos por microcalorimetria: III interação de m-alcoxifenóis e p-hidroxibenzoatos de alquila com Escherichia coli

QSAR studies based on flow microcalorimetric bioassay data for interaction of homologous series of m-alkoxyphenols and p-hydroxybenzoates with E. coli cells were carried out applying factorial design. Results for both series showed a linear relationship between log(dose)max and log Po/w. Analysis of these data allows the identification of contributions toward the derived bioactivity from the parent structures (the molecule minus n-CH2 groups present in the side-chain) and the lipophilic groups, CH2. These results are discussed with respect to drug quantitative structure-relationship.

Stereoselective sodium borohydride reductions of cyclopentanones: influence of ceric chloride on the stereochemistry of reaction

In this paper we describe the reduction by NaBH4 of some cyclopentanones containing an oxygenated function at the side chain position beta to the carbonyl group, both in the presence and in the absence of CeCl3. Some suggestions for the rationalization of the results are discussed, considering the stereochemical course of the reactions.

Preparation and phytotoxicity of sorgoleone analogues

3,5-Dimethoxybenzylic alcohol was converted into the 2-acetoxy-5-methoxy-3-(pent-1-yl)-1,4-benzoquinone (12), in seven steps, with an overall yield of 14.6%. The natural quinone sorgoleone (1) was isolated from Sorghum bicolor and converted into the corresponding quinone (13) having a saturated side chain. The selective effects of these compounds (1, 12 and 13), at the dose of 5.6 mug of a.i./ g of substrate, on the growth of Cucumis sativus, Lactuca sativa, Desmodium tortuosum, Hyptis suaveolens and Euphorbia heterophylla were evaluated. All three compounds caused some inhibition on the root growth of the test plants (0.0-69.19%) with the aerial parts less affected. The results showed that the triene unit of the sorgoleone side chain is not essential for the phytotoxicity and also the synthetic quinone was as active as the natural product.

Análise de glicocorticosteróides por CG-EM: uma nova abordagem de derivatização para o controle de dopagem no esporte

Glucocorticosteroids (CT) show a powerful anti-inflammatory effect. In view of this, they are extensively used in sports medicine, but their misuse (systemic administration) can lead to severe injuries on athletes and has been restricted by the IOC in recent years. For GC-MS analysis, a derivatization step is necessary in order to convert them to a stable form, thus preventing thermal breakdown with the loss of the ketone side chain. Derivatization of CT is reviewed and a new approach of silylation is presented for screening of CT in urine.

Estudo da estrutura e da solvatação do HNP-3, um antibiótico natural, por dinâmica molecular

The structure and hydration of the HNP-3 have been derived from molecular dynamics data using root mean square deviation, radial and energy distributions. Three antiparallel beta sheets were found to be preserved. 15 intramolecular hydrogen bonds were identified together with 36 hydrogen bonds on the backbone and 35 on the side chain atoms. From the point of view of the hydration dynamics, the analysis shows a high solvent accessibility of the monomer and attractive interactions with water molecules.

Polarizabilidade atômica efetiva alfad pode ditar a ionização de radioligantes 99Tc m - diaminoditiol alquilamínicos?

Polarizability correlates well with organic ion stabilization in solution and can be defined as a measure of the relative ease of the distortion of the electronic cloud of a dipolar system exposed to an external electric field. The effective atomic polarizability, alphad, has a fundamental influence on chemical reactivity in the gas phase and in solution. In terms of chemical reactivity the charge is generated within the molecule as a positive charge due to protonation, ionization or resulting from the attack of a nucleophilic anion. In this paper, lipoidal diaminedithiol (DADT) perfusion radioligands based on 99Tc m and possessing an alkylamine side chain have been used to check the influence of alphad on their brain uptake. Some new DADT derivatives, respectively DADT-DIPA (diaminedithiol - diisopropylamine), DADT DIBA (diaminedithiol diisobutylamine), DADT-PR (diaminedithiol - branched pyperidine), have been designed to have high nitrogen alkylamine alphad values. In spite of the fact of higher alphad values having been correlated to higher brain uptakes, there isn't a clear mechanism able to trap these radioligands into the brain space.

Efecto del catión, del anión y del co-ión sobre la agregación de líquidos iónicos en solución acuosa

The aggregation behavior of thirteen 1-alkyl-3-methylimidazolium based ionic liquids in aqueous solution is presented, considering variations of the alkyl side chain length as well as the anionic moiety. Cation and anion molecular volumes are selected as appropriate molecular descriptors. Additionally, the existing relationship between critical micelle concentration (CMC) and electrolyte concentration in solution is established, aiming to clarify ion effects. CMC values were obtained by measuring electrical conductivity and surface tension. It was confirmed that aggregation of ionic liquids in aqueous solution and in presence of inorganic salts is affected by the factors developed in this study.

DERIVATIZACIÓN Y CARACTERIZACIÓN ESPECTROSCÓPICA DE UN BIOPOLÍMERO A BASE DE L -LISINA CON ANÁLOGOS DE LA D-BIOTINA: CO -POLI(L-LISINA)-GRAFT -(ε-N-[X-D -BIOTINIL]-L-LISINA)

We report the single-step derivatization reaction of a biopolymer based onL -lysine with D -biotin analogs:Co -poly(L -lysine)-graft-(ε-N -[X-D-biotinyl]-L -lysine) (PLL-X-Biotin). The valeric acid carboxylate of D -biotin is activated to an NHS ester for direct modification of amine groups in proteins and other macromolecules. NHS esters react by nucleophilic attack of an amine in the carbonyl group, releasing the NHS group, and forming a stable amide linkage. NHS-X-Biotin is the simplest biotinylation reagent commercially available. In contrast withD -biotin, it has a longer spacer arm off the valeric acid side chain allowing better binding potential for avidin or streptavidin probes. Derivatization of poly(L -lysine) (PLL) with NHS-X-Biotin led to a copolymer PLL-X-Biotin. UV-Visible, IR-FT and 1H NMR characteristics derived from synthesis are briefly discussed.

Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12%) were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas) occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone) from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate). This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes

Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compund was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD50 of 30 µM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis.

Effects of grilling on cholesterol oxide formation and fatty acids alterations in fish

Due to the adverse effects of the cholesterol oxidation products for the human health, the search of the occurrence and the quantification of these compounds in foods are considered of great importance. In this paper the effect of grilling in hake and sardine on cholesterol oxides formation and fatty acids alterations was investigated. The main fatty acids determined in both fishes were docosahexaenoic (DHA), oleic, eicosapentaenoic (EPA) and palmitoleic. The total lipids, fatty acids and cholesterol contents were decreased significantly (p < 0.02) after thermal treatment, with simultaneous increase of the cholesterol oxides contents. The cholesterol oxides determined in both species in the present study were: 19-hydroxycholesterol, 24(S)-hydroxycholesterol, 22(S) hydroxycholesterol, 25-hydroxycholesterol, 25(R)-hydroxycholesterol and 7-ketocolesterol. Besides the presence of the cholesterol oxides in raw fishes, there were a greater number of products resulting from the oxidation of cholesterol side chain, a fact rarely observed in foods.

Secretory TAT-peptide-mediated protein transduction of LIF receptor α-chain distal cytoplasmic motifs into human myeloid HL-60 cells

The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3) can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML) cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss) inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO) cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05) 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.

Supply chain management

Nos últimos anos, a economia mundial e a economia brasileira têm sofrido mudanças importantes. Fusões, aquisições e alianças estratégicas têm se multiplicado. Parte considerável destas mudanças relaciona-se com profundas alterações nos sistemas de valores de todos os segmentos industriais. A busca da competitividade relaciona-se cada vez mais com a busca do ótimo sistêmico além das fronteiras da empresa. Neste contexto, a administração logística ganha nova dimensão, envolvendo a integração de todas as atividades ao longo da cadeia de valores e do sistema de valores, das matérias-primas ao cliente final. O objetivo deste trabalho é (re)situar a administração logística no contexto de mudanças, enfatizando a metodologia da gestão da cadeia de demanda (supply chain management).