A novel diselenide attenuates the carrageenan-induced inflammation by reducing neutrophil infiltration and the resulting tissue damage in mice.

Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the in vitro and in vivo anti-inflammatory activity of a novel diselenide named as dibenzyl[diselanediyIbis(propane-3-1diyl)] dicarbamate (DD). DD reacted with HOCl (k = 9.2 x 107 M-1s-1), like glutathione (k = 1.2 x 108 M-1s-1), yielding seleninic and selenonic acid derivatives, and it also decreased HOCl formation by activated human neutrophils (IC50=4.6 µM) and purified myeloperoxidase (MPO) (IC50=3.8 µM). However, tyrosine, MPO-I and MPO-II substrates, did not restore HOCl formation in presence of DD. DD inhibited the oxidative burst in dHL-60 cells with no toxicity up to 25 µM for 48h. Next, an intraperitoneal administration of 25, 50, and 75 mg/kg DD decreased total leukocyte, neutrophil chemotaxis, and inflammation markers (MPO activity, lipid peroxidation, albumin exudation, nitrite, TNF-α, IL-1ß, CXCL1/KC, and CXCL2/MIP-2) on a murine model of carrageenan-induced peritonitis. Likewise, 50 mg/kg DD (i.p.) decreased carrageenan-induced paw edema over 5h. Histological and immunohistochemistry analyses of the paw tissue showed decreased neutrophil count, edema area, and MPO, carbonylated, and nitrated protein staining. Furthermore, DD treatment decreased the fMLP-induced chemotaxis of human neutrophils (IC50=3.7 µM) in vitro with no toxicity. Lastly, DD presented no toxicity in a single-dose model using mice (50 mg/kg, i.p.) over 15 days and in Artemia salina bioassay (50 to 2000 µM), corroborating findings from in silico toxicological study. Altogether, these results demonstrate that DD attenuates carrageenan-induced inflammation mainly by reducing neutrophil migration and the resulting damage from MPO-mediated oxidative burst.

Stability of di-butyl-dichalcogenide-capped gold nanoparticles: experimental data and theoretical insights.

Metals capped with organochalcogenides have attracted considerable interest due to their practical applications, which include catalysis, sensing, and biosensing, due to their optical, magnetic, electrochemical, adhesive, lubrication, and antibacterial properties. There are numerous reports of metals capped with organothiol molecules; however, there are few studies on metals capped with organoselenium or organotellurium. Thus, there is a gap to be filled regarding the properties of organochalcogenide systems which can be improved by replacing sulfur with selenium or tellurium. In the last decade, there has been significant development in the synthesis of selenium and tellurium compounds; however, it is difficult to find commercial applications of these compounds because there are few studies showing the feasibility of their synthesis and their advantages compared to organothiol compounds. Stability against oxidation by molecular oxygen under ambient conditions is one of the properties which can be improved by choosing the correct organochalcogenide; this can confer important advantages for many more suitable applications. This paper reports the successful synthesis and characterization of gold nanoparticles functionalized with organochalcogenide molecules (dibutyl-disulfide, dibutyl-diselenide and dibutyl-ditelluride) and evaluates the oxidation stability of the organochalcogenides. Spherical gold nanoparticles with diameters of 24 nm were capped with organochalcogenides and were investigated using X-ray photoelectron spectroscopy (XPS) to show the improved stability of organoselenium compared with organothiol and organotellurium. The results suggest that the organoselenium is a promising candidate to replace organothiol because of its enhanced stability towards oxidation by molecular oxygen under ambient conditions and its slow oxidation rate. The observed difference in the oxidation processes, as discussed, is also in agreement with theoretical calculations.

Synthesis, biophysical and functional studies of two BP100 analogues modified by a hydrophobic chain and a cyclic peptide.

Antimicrobial peptides (AMPs) work as a primary defense against pathogenic microorganisms. BP100, (KKLFKKILKYL-NH2), a rationally designed short, highly cationic AMP, acts against many bacteria, displaying low toxicity to eukaryotic cells. Previously we found that its mechanism of action depends on membrane surface charge and on peptide-to-lipid ratio. Here we present the synthesis of two BP100 analogs: BP100­alanyl­hexadecyl­1­amine (BP100-Ala-NH-C16H33) and cyclo(1­4)­d­Cys1, Ile2, Leu3, Cys4-BP100 (Cyclo(1­4)­cILC-BP100). We examined their binding to large unilamellar vesicles (LUV), conformational and functional properties, and compared with those of BP100. The analogs bound to membranes with higher affinity and a lesser dependence on electrostatic forces than BP100. In the presence of LUV, BP100 and BP100-Ala-NH-C16H33 acquired α-helical conformation, while Cyclo(1­4)­cILC-BP100) was partly α-helical and partly ß-turn. Taking in conjunction: 1. particle sizes and zeta potential, 2. effects on lipid flip-flop, 3. leakage of LUVs internal contents, and 4. optical microscopy of giant unilamellar vesicles, we concluded that at high concentrations, all three peptides acted by a carpet mechanism, while at low concentrations the peptides acted by disorganizing the lipid bilayer, probably causing membrane thinning. The higher activity and lesser membrane surface charge dependence of the analogs was probably due to their greater hydrophobicity. The MIC values of both analogs towards Gram-positive and Gram-negative bacteria were similar to those of BP100 but both analogues were more hemolytic. Confocal microscopy showed Gram-positive B. subtilis killing with concomitant extensive membrane damage suggestive of lipid clustering, or peptide-lipid aggregation. These results were in agreement with those found in model membranes.

Stability Study of Hypervalent Tellurium Compounds in Aqueous Solutions.

Hypervalent tellurium compounds (telluranes) are promising therapeutical agents with negligible toxicities for some diseases in animal models. The C-Te bond of organotellurium compounds is commonly considered unstable, disfavoring their applicability in biological studies. In this study, the stability of a set of telluranes composed of an inorganic derivative and noncharged and charged organic derivatives was monitored in aqueous media with 1H, 13C, and 125Te NMR spectroscopy and high-resolution mass spectrometry. Organic telluranes were found to be remarkably resistant and stable to hydrolysis, whereas the inorganic tellurane AS101 is totally converted to the hydrolysis product, trichlorooxytellurate, [TeOCl 3 ]-, which was also observed in the hydrolysis of TeCl 4 . The noteworthy stability of organotelluranes in aqueous media makes them prone to further structure-activity relationship studies and to be considered for broad biological investigations.

Antiproliferative and ultrastructural effects of phenethylamine derivatives on promastigotes and amastigotes of Leishmania (Leishmania) infantum chagasi.

Leishmania (Leishmania) infantum chagasi is one of the agents that cause visceral leishmaniasis. This disease occurs more frequently in third world countries, such as Brazil. The treatment is arduous, and is dependent on just a few drugs like the antimonial derivatives and amphotericin B. Moreover, these drugs are not only expensive, but they can also cause severe side effects and require long-term treatment. Therefore, it is very important to find new compounds that are effective against leishmaniasis. In the present work we evaluated a new group of synthetic amides against the promastigote and amastigote forms of L. infantum chagasi. The results showed that one of these amides in particular, presented very effective activity against the promastigotes and amastigotes of L. infantum chagasi at low concentrations and it also presented low toxicity for mammal cells, which makes this synthetic amide a promising drug for combating leishmaniasis.

Unraveling the Organotellurium Chemistry Applied to the Synthesis of Gold Nanomaterials.

Long-term preservation of the properties of gold nanoparticles in both solution and the dry powder form can be difficult. We have overcome this challenge by using organotellurium derivatives as both reducing agents and stabilizers in the synthesis of gold nanoparticles. This new synthetic protocol takes advantage of the photochemical and oxidative properties of diphenyl ditelluride (Ph2Te2), which, so far, have never been exploited in the synthesis of gold nanoparticles. The Au/Te core/shell (inorganic/organic) hybrid nanomaterial can be obtained in a one-step reaction, using only Ph2Te2 and HAuCl4. By modifying the reaction conditions, different resonance conditions of the gold core are achieved due to the formation of external shells with different thicknesses. The organotellurium shell can be easily removed by resuspension of the nanoparticles in environmentally friendly solvents, such as water or ethanol, making the Au core available for subsequent applications. A mechanism for the formation of core/shell nanoparticles has also been discussed.

Helical Poly(phenylacetylene) Bearing Chiral and Achiral Imidazolidinone-Based Pendants that Catalyze Asymmetric Reactions due to Catalytically Active Achiral Pendants Assisted by Macromolecular Helicity.

A series of optically active helical copolymers of phenylacetylenes are prepared by the rhodium-catalyzed copolymerization of the imidazolidinone-linked, catalytically active achiral phenylacetylenes and catalytically inactive chiral phenylacetylenes. The obtained chiral/achiral copolymers exhibit an induced circular dichroism in the UV-vis regions of the copolymer backbones resulting from a preferred-handed helical conformation biased by the chiral imidazolidinone units incorporated in the copolymers. The copolymers are found to catalyze the asymmetric Diels-Alder reaction and produce the products with a moderate enantioselectivity in spite of the fact that the catalytically active units of the copolymers are achiral, indicating that the observed enantioselectivity totally originates from the helical chirality dynamically induced by the optically active, but catalytically inactive imidazolidinone units incorporated in the copolymers.

Evaluation of a special combination of glucan with organic selenium derivative in different murine tumor models.

ß-glucans are well-established immunomodulators with strong effects resulting in slowing or even inhibiting cancer growth. Recent studies have repeatedly suggested that the biological activities of ß-glucan can be potentiated by the addition of other bioactive agents. In the current study, we focused on the anticancer effects of a combination of yeast-derived ß-glucan and a selenium-linked pseudodisaccharide. Using three different models of murine cancer, we showed that this combination strongly suppressed the growth of all three types of cancers, most likely via the interaction with natural anticancer antibodies.

Synthetic organotelluride compounds induce the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisiae.

BACKGROUND: Resistance to fluconazole, a commonly used azole antifungal, is a challenge for the treatment of fungal infections. Resistance can be mediated by overexpression of ABC transporters, which promote drug efflux that requires ATP hydrolysis. The Pdr5p ABC transporter of Saccharomyces cerevisiae is a well-known model used to study this mechanism of antifungal resistance. The present study investigated the effects of 13 synthetic compounds on Pdr5p. RESULTS: Among the tested compounds, four contained a tellurium-butane group and shared structural similarities that were absent in the other tested compounds: a lateral hydrocarbon chain and an amide group. These four compounds were capable of inhibiting Pdr5p ATPase activity by more than 90%, they demonstrated IC50 values less than 2 µM and had an uncompetitive pattern of Pdr5p ATPase activity inhibition. These organotellurides did not demonstrate cytotoxicity against human erythrocytes or S. cerevisiae mutant strains (a strain that overexpress Pdr5p and a null mutant strain) even in concentrations above 100 µM. When tested at 100 µM, they could reverse the fluconazole resistance expressed by both the S. cerevisiae mutant strain that overexpress Pdr5p and a clinical isolate of Candida albicans. CONCLUSIONS: We have identified four organotellurides that are promising candidates for the reversal of drug resistance mediated by drug efflux pumps. These molecules will act as scaffolds for the development of more efficient and effective efflux pump inhibitors that can be used in combination therapy with available antifungals.

A one-pot glycerol-based additive-blended ethyl biodiesel production: a green process.

N-methyl-2-pyrrolidonium methyl sulfonate, a Brønsted acid ionic liquid, promoted the transesterification of soybean oil with ethanol giving a high quality fatty acid ethyl ester. At the end of the reaction, after distillation of excess of ethanol, spontaneous phase separation took place. While the clear upper phase corresponded to the ethyl ester, the lower phase was composed of a mixture of glycerol byproduct and the catalyst. By addition of a stoichiometric amount of appropriated reagents to the resulting mixture, a new ionic liquid-catalyzed process allows the conversion of the glycerol into less polar derivatives, and consequent migration to the ethyl esters phase. This work demonstrated that emulsion, phase separation and contamination problems were completely avoided and the glycerol could be incorporated into the biodiesel as additives in a single step. The whole process involves two renewable starting materials, ethanol and vegetable oil, allowing a total green additive-blended biodiesel production process.

Antioxidant effect of functionalized alkyl-organotellurides: a study in vitro.

We evaluated the in vitro antioxidant effect of alkyl-organotellurides A-D on lipid peroxidation and protein carbonylation in rat liver homogenates. The thiol oxidase and thiol peroxidase-like activities of compounds were investigated. delta-Aminolevulinic acid dehydratase (delta-ALA-D) activity was determined in rat liver homogenates. Compounds A-D protected against lipid peroxidation induced by Fe(2+)/EDTA and sodium nitroprusside (SNP). According to the confidence limits of the IC(50) values of compounds A-D, the IC(50) values for organotellurides followed the order: C (0.30 microM) < or = B (0.40 microM) < D (0.68 microM) < A (2.90 microM), for Fe(2+)/EDTA, and B (0.21 microM) < or = C (0.33 microM) < or = D (0.43 microM) < A (1.21 microM) for SNP-induced lipid peroxidation. Compounds A-D reduced protein carbonyl content to control levels. The results demonstrated an inverse correlation between thiol oxidase and delta-ALA-D activities. This study supports an antioxidant effect of organotellurides A-D on rat liver.

2-Cyclo-hexyl-4-methyl-tetra-hydro-pyran-4-ol.

In the title compound, C(12)H(22)O(2), the 4-methyl-tetra-hydro-pyran-4-ol ring adopts a conformation close to that of a chair and with the two O atoms syn; the cyclo-hexyl group occupies an equatorial position and adopts a chair conformation. In the crystal packing, supra-molecular chains along the b axis are sustained by O-H⋯O hydrogen bonds. These are connected into undulating layers in the ab plane by C-H⋯O inter-actions.