Preparation and antitubercular activity of lipophilic diamines and amino alcohols

A series of diamines and amino alcohols derived from 1-dodecanol, 1-tetradecanol, 1,2-dodecanediol and 1,2-tetradecanediol were synthesized and tested for their antitubercular activity. Compounds 3, 8 and 9 were found to be the most active (MIC of 6.25 ¼g/mL). Nine other compounds displayed activity against Mycobacterium tuberculosis, with a MIC of 12.5 ¼g/mL.

Electrochemical evaluation of lipophilic antioxidants from Iryanthera juruensis fruits (Myristicaceae)

TLC autographic assays revealed in the hexane extract of Iryanthera juruensis (Myristicaceae) the presence of two compounds, with antioxidant properties towards beta-carotene. They were isolated and identified as 3-methyl-sargachromenol (1) and sargachromenol (2). Further investigation of the hexane extract led to isolations of 3-methyl-sargaquinoic acid (3) and sargaquinoic acid (4). The electrochemical behaviour of these compounds was studied in CH2Cl2/Bu4NBF4 at glassy carbon electrode. The phenolic group in both tocotrienols 1 and 2 are oxidized at +0.23V and +0.32V and their oxidation potentials are correlated with the observed antioxidant activities and oxidation mechanism of alpha-tocopherol. The reductive voltametric behaviour of quinone function in both plastoquinones 3 and 4 is discussed.

Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [99mTc(MIBI)6]+

Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI)6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI)6]+ since impurities such as99mTc-reduced-hydrolyzed (RH),99mTcO4- and [99mTc(cysteine)2]-complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

Transport pathways in the malaria-infected erythrocyte: characterization and their use as potential targets for chemotherapy

The intraerythrocytic malarial parasite is involved in an extremely intensive anabolic activity while it resides in its metabolically quiescent host cell. The necessary fast uptake of nutrients and the discharge of waste product, are guaranteed by parasite-induced alterations of the constitutive transporters of the host cell and the production of new parallel pathways. The membrane of the host cell thus becomes permeable to phospholipids, purine bases and nucleosides, small non-electrolytes, anions and cations. When the new pathways are quantitatively unimportant, classical inhibitors of native transporters can be used to inhibit parasite growth. Several compounds were found to effectively inhibit the new pathways and consequently, parasite growth. The pathways have also been used to introduce cytotoxic agents. The parasitophorous membrane consists of channels which are highly permeable to small solutes and display no ion selectivity. Transport of some cations and anions across the parasite membrane is rapid and insensitive to classical inhibitors, and in some cases it is mediated by specific antiporters which respond to their respective inhibitors. Macromolecules have been shown to reach the parasitophorous space through a duct contiguous with the host cell membrane, and subsequently to be endocytosed at the parasite membrane. The simultaneous presence of the parasitophorous membrane channels and the duct, however, is incompatible with experimental evidences. No specific inhibitors were found as yet that would efficiently inhibit transport through the channels or the duct.

Modulatory effect of iron chelators on adenosine deaminase activity and gene expression in Trichomonas vaginalis

Trichomonas vaginalis is a flagellate protozoan that parasitises the urogenital human tract and causes trichomoniasis. During the infection, the acquisition of nutrients, such as iron and purine and pyrimidine nucleosides, is essential for the survival of the parasite. The enzymes for purinergic signalling, including adenosine deaminase (ADA), which degrades adenosine to inosine, have been characterised in T. vaginalis. In the evaluation of the ADA profile in different T. vaginalisisolates treated with different iron sources or with limited iron availability, a decrease in activity and an increase in ADA gene expression after iron limitation by 2,2-bipyridyl and ferrozine chelators were observed. This supported the hypothesis that iron can modulate the activity of the enzymes involved in purinergic signalling. Under bovine serum limitation conditions, no significant differences were observed. The results obtained in this study allow for the assessment of important aspects of ADA and contribute to a better understanding of the purinergic system in T. vaginalis and the role of iron in establishing infection and parasite survival.

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.

Estratégias para a síntese de desoxinucluosídeos

The number of agents available for the treatment of viral infections has increased dramatically during the past decade most of them belonging to the nucleoside class. The accomplishment of many syntheses for these nucleosides in recent years offers evidence that the field is very important for the organic synthesis. The discussion of several approaches for preparing deoxy and dehydronucleosides is reviewed in a simplified way.

Optimisation of the lipase-catalysed preparation of a nucleoside prodrug model using an experimental design methodology

The preparation of 2', 3'-di-O-hexanoyluridine (2) by a Candida antarctica B lipase-catalysed alcoholysis of 2', 3', 5'-tri-O-hexanoyluridine (1) was optimised using an experimental design. At 25 ºC better experimental conditions allowed an increase in the yield of 2 from 80% to 96%. In addition to the yield improvement, the volume reaction could be diminished in a factor of 5 and the reaction time significantly shortened.

Constituintes químicos da ascídia didemnum psammatodes (sluiter, 1895) coletada na costa cearense

Chemical investigation of the methanolic extract of the ascidian Didemnum psammatodes has led to the identification of the nucleosides 2'-deoxyuridine (1), thymidine (2), 2'-deoxyinosine (3) and 2'-deoxyguanosine (4), the steroids cholestanol, cholestanone and stigmasterol in mixture and batyl alcohol plus two analogs, 1-heptadecyloxy-2,3-propanediol and 1-nonadecyloxy-2,3-propanediol in mixture. Their structures were proposed by NMR, MS and comparison with literature data and GC-MS analysis.

Políticas públicas e o empreendedorismo em química no Brasil: o caso da Microbiológica

Microbiológica is a science-based Brazilian Company with its core competence focused on nucleoside process chemistry. This article describes its origin and contributions as well as comments on public policies which impact the Brazilian industrial development.

Nanopartículas de lipídios sólidos: métodos clássicos de produção laboratorial

Solid lipid nanoparticles have been extensively investigated as drug delivery systems. These colloidal systems have major advantages compared to others more traditional. Reported advantages include sustained release, ability to solubilize lipophilic drugs, increased physical and chemical stability of labile molecules, decreased unwanted side-effects showing lower toxicity, and scale up facilities. This paper aims at reviewing the traditional methods of solid lipid nanoparticles production, such as fusion-emulsification (hot and cold), solvent evaporation-emulsification and microemulsion, dealing with the main technological parameters that influence the quality properties of solid lipid nanoparticles.

Estudos de QSAR 2D baseados em descritores topológicos e fragmentos moleculares para uma série de derivados azólicos ativos contra Candida albicans

Azole derivatives are the main therapeutical resource against Candida albicans infection in immunocompromised patients. Nevertheless, the widespread use of azoles has led to reduced effectiveness and selection of resistant strains. In order to guide the development of novel antifungal drugs, 2D-QSAR models based on topological descriptors or molecular fragments were developed for a dataset of 74 molecules. The optimal fragment-based model (r² = 0.88, q² = 0.73 and r²pred = 0.62 with 6PCs) and descriptor-based model (r² = 0.82, q² = 0.79 and r²pred = 0.70 with 2 PCs), when analysed synergically, suggested that the triazolone ring and lipophilic properties are both important to antifungal activity.

MICROEMULSÕES: COMPONENTES, CARACTERÍSTICAS, POTENCIALIDADES EM QUÍMICA DE ALIMENTOS E OUTRAS APLICAÇÕES

Microemulsions (MEs) are thermodynamically stable systems consisting of nanosized droplets dispersed in a solvent continuous medium (known as pseudo-phase), which is immiscible with the dispersed phase. These systems consist of water, a hydrophobic solvent called "oil," an amphiphile and often, a co-surfactant that is normally a medium chain alcohol. A large number of publications describe the importance of MEs in many branches of chemistry, and there is an intensive search for new applications. In addition, MEs have been applied in many areas, including oil extraction, removal of environmental pollutants from soils and effluents, dissolution of additives in lubricants and cutting oils, cleaning processes, dyeing and textile finishing, as nanoreactors to obtain nanoparticles of metals, semiconductors, superconductors, magnetic and photographic materials, and latex. However, only some studies indicate the potential applications of MEs in food and even fewer evaluate their chemical behavior. Potential applications of MEs in food comprise dissolution of lipophilic additives, stabilization of nutrients and biologically active compounds, using as an antimicrobial agent and to maximize the efficiency of food preservatives. This work consists of a literature review focusing on composition and physical and chemical characteristics of microemulsions. Despite the small number of studies on the subject reported in the literature, we demonstrate some potential applications of MEs in food chemistry.

CROMATOGRAFIA POR INTERAÇÕES HIDROFILICAS (HILIC): ESTADO DA ARTE E APLICAÇÕES

Hydrophilic interaction liquid chromatography (HILIC) has been gaining increased attention for its effective separation of highly polar compounds, which include carbohydrates, amino acids, pharmaceutical compounds, proteins, glycoproteins, nucleosides, etc. Polar compounds are usually poorly retained on reverse-phase liquid chromatography (RP-HPLC) columns or have poor solubility in the apolar mobile phase of normal-phase high performance liquid chromatography (NP-HPLC). Since HILIC uses organic solvents such as ACN or MeOH ( > 70%), also used in RP-HPLC and polar stationary phases similar to NP-HPLC (bare silica, diol, amino, amide, saccharide, zwitterionic stationary phases, etc.), it represents a hybrid of the two separation modes. The high organic content in the MP leads to good compatibility with mass spectrometry (MS), increasing the detectivity. This review describes the fundamentals of HILIC and highlights some interesting applications.

Foliar anatomy and histochemistry in seven species of Eucalyptus

This work aimed to describe the foliar anatomy of seven species of Eucalyptus, emphasizing the characterization of secretory structures and the chemical nature of the compounds secreted and /or present in the leaves. Anatomical characterization and histochemical evaluation to determine the nature and localization of the secondary compounds were carried out in fully expanded leaves, according to standard methodology. Anatomical differences were verified among the species studied, especially in E. pyrocarpa. Sub-epidermal cavities were the only secretory structures found in the seven species studied, with higher density in E. pellita and lower in E. pilularis. The following compounds were histochemically detected: lipophilic compounds, specifically lipids of the essential or resin-oil type and sesquiterpene lactones found in the lumen of the cavities of the seven species; and hydrophilic compounds, of the phenolic compound type found in the mesophyll of all the species studied and on the epidermis of some of them. The results confirmed the complexity of the product secreted by the cavities, stressing the homogeneous histochemistry nature of these compounds among the species. However, the phenolic compounds results may be an indication of important variations in adaptations and ecological relations, since they show differences among the species.