Search

A transition metal-free method for de novo construction of diverse sulfonated pyrazoles from readily available sulfonyl hydrazides, 1,3-diketones, and sodium sulfinates was established under mild conditions. Pyrazoles bearing two different sulfonyl groups were obtained in one step. The method features a diversity of substituents of the pyrazole products and a remarkably simple work-up.

Malaria i a serious health problem caused by Plasmodium spp. that can be treated by an anti-folate pyrimethamine (PYR) drug. Deferiprone (DFP) is an oral iron chelator used for the treatment of iron overload and has been recognized for its potential anti-malarial activity. Deferiprone-resveratrol hybrids (DFP-RVT) have been synthesized to present therapeutic efficacy at a level which is superior to DFP. We have focused on determining the lipophilicity, toxicity and inhibitory effects on P. falciparum growth and the iron-chelating activity of labile iron pools (LIPs) by DFP-RVT. According to our findings, DFP-RVT was more lipophilic than DFP ( p < 0.05) and nontoxic to blood mononuclear cells. Potency for the inhibition of P. falciparum was PYR > DFP-RVT > DFP in the 3D7 strain (IC 50 = 0.05, 16.82 and 47.67 µM, respectively) and DFP-RVT > DFP > PYR in the K1 strain (IC 50 = 13.38, 42.02 and 105.61 µM, respectively). The combined treatment of DFP-RVT with PYR additionally enhanced the PYR activity in both strains. DFP-RVT dose-dependently lowered LIP levels in PRBCs and was observed to be more effective than DFP at equal concentrations. Thus, the DFP-RVT hybrid should be considered a candidate as an adjuvant anti-malarial drug through the deprivation of cellular iron.

A selective and efficient synthesis of diaryl 1,3,5-oxadiazines was established for the first time from simple and readily available amidines in wet DMSO. DMSO was employed as a dual carbon synthon and water offered the oxygen atom to construct the oxadiazine ring. The reaction involved two new C-N and two new C-O bond formations.

A convenient one-pot, three-component reaction has been developed for the synthesis of 3-aroylimidazo[1,2- a ]- N -heterocycles from aryl ketones and 2-amino- N -heterocycles using dimethyl sulfoxide as a methylene donor. The reaction proceeds smoothly catalyzed by I 2 in the presence of K 2 S 2 O 8 and affords the desired products in moderate to good yields. This protocol offers significant superiority in accessing biologically active 3-aroylimidazo[1,2- a ]- N -heterocycles with various substitution patterns.

A one-pot, four-component annulation of 2,3,4,6-tetraarylpyridines from aromatic aldehydes, methyl ketones, diaryl ethanones, and ammonium acetate is described. The reaction features high functional group compatibility in air under solvent-free conditions without any additive and only water as the nontoxic byproduct, providing a strategy for the facile, economical, and eco-friendly construction of multiaryl-substituted pyridines from simple and readily available reactants.

A simple and practical domino protocol for the selective synthesis of 2-aroylbenzothiazoles and 2-aryl benzothiazoles catalyzed by I 2 is developed under metal-free conditions. The reaction outcomes are exclusively controlled by the reaction oxidant/medium. With DMSO employed as both the solvent and the oxidant, an oxidation of aromatic methyl ketones takes precedence over the condensation with 2-aminobenzenethiols. On the other hand, when the reaction was carried out in PhNO 2 or in 1,4-dioxane containing PhNO 2 , the condensation of aromatic methyl ketones with 2-aminobenzenethiols has priority to form imines which is followed by an oxidation of the methyl group from ketones to afford 2-arylbenzothiazoles as a sole product. The PhNO 2 /I 2 co-catalytic system is proposed first time.

1,2-Dihydro-1,3,5-triazines and symmetrical 1,3,5-triazines were obtained in up to 81% yields from amidines and N,N-dimethylethanolamine catalyzed by CuCl2. The reaction involves three C-N bond formations during the oxidative annulation process and the mechanism was proposed. This efficient synthesis of 1,2-dihydro-1,3,5-triazines was developed for the first time.

An efficient method for the synthesis of 3-functionalized quinolines from commercially available acetophenones and anthranil has been described. Selectfluor propels the C(sp 3 )-H bond activation of the acetophenones and aza-Michael addition of anthranil resulting in annulated 3-acylquinolines in moderate to high yields. DMSO acts not only as a solvent but also as a one carbon donor in the reaction., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Nontransferrin-bound iron (NTBI) is a heterogeneously speciated plasma iron, typically detectable when transferrin saturation (TfSat) exceeds 75%. Here, we examine factors affecting NTBI levels by a recently discovered direct chelator-based (CP851) fluorescent bead-linked flow-cytometric assay (bead-NTBI), compared with the established indirect nitrilotriacetate (NTA) assay in 122 iron-overloaded patients, including 64 on recent iron chelation therapy and 13 healthy volunteers. Both methods correlated (r = 0.57, P < 0.0001) but with low agreement, attributable to 2 major factors: (1) the NTA method, unlike the bead method, is highly dependent on TfSat, with NTBI under-estimation at low TfSat and over-estimation once Tf is saturated, (2) the bead method detects <3-fold higher values than the NTA assay in patients on recent deferiprone-containing chelation due to greater detection of chelate complexes but lower values for patients on deferasirox. The optimal timing of sample collection relative to chelation dosing requires further study. Patients with splenectomy, high-storage iron, and increased erythropoiesis had greater discrepancy between assays, consistent with differential access by both methods to the NTBI pools associated with these clinical variables. The bead-NTBI assay has advantages over the NTA assay, being less dependent on TfSat, hence of less tendency for false-negative or false-positive values at low and high TfSat, respectively., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

We report the synthesis and characterization of a fluorescent iron chelator (4), shown to be effective in inhibiting the growth of Mycobacterium avium in macrophages, together with the synthesis and characterization of two unsuccessful analogues selected to facilitate identification of the molecular properties responsible for the antimicrobial activity. Partition of the chelators in liposomes was investigated and the compounds were assessed with respect to uptake by macrophages, responsiveness to iron overload/iron deprivation and intracellular distribution by flow cytometry and confocal microscopy. The synthesis of the hexadentate chelators is based on a tetrahedral structure to which three bidentate 3-hydroxy-4-pyridinone chelating units are linked via amide bonds. The structure is synthetically versatile, allowing further addition of functional groups such as fluorophores. Here, we analyse the non-functionalized hexadentate unit (3) and the corresponding rhodamine B (4) and fluorescein (5) labelled chelators. The iron(III) stability constant was determined for 3 and the values log beta = 34.4 and pFe(3+) = 29.8 indicate an affinity for iron of the same order of magnitude as that of mycobacteria siderophores. Fluorescence properties in the presence of liposomes show that 4 strongly interacts with the lipid phase, whereas 5 does not. Such different behaviour may explain their distinct intracellular localization as revealed by confocal microscopy. The flow cytometry and confocal microscopy studies indicate that 4 is readily engulfed by macrophages and targeted to cytosol and vesicles of the endolysosomal continuum, whereas 5 is differentially distributed and only partially colocalizes with 4 after prolonged incubation. Differential distribution of the compounds is likely to account for their different efficacy against mycobacteria.

Objective: To observe the variety of fat analysis of prepackaged foods from different labs of China., Methods: Thirteen foods from seven kinds were selected as food samples: cereal products, bean products, meat products, dairy products, beverages, nuts, snacks, according to national prepackaged foods consumption survey results in 2000. The sample fat contents were analyzed parallelly for three times by national standard methods in seven labs from all the country., Results: The 93.4% of results were up to grade by Grubbs, Cochran and Dixon screening methods. The accuracy of fat analysis was expressed by variety coefficiency (C. V%). The C. V% of inner labs and inter labs were from 1.89% to 5.39% and from 2.64% to 24.14%, the total and average C. V% level were from 3.32% to 24.60% and 11.51%. Besides the fish tin and fat-free milk powder (with very low fat content), the relative expanded uncertainties of fat detection were from 6.48% to 34.80% (average 17.62%)., Conclusion: Fat analysis level in labs from all the country was fit for national standards. If fat labeling were focused on its middle and high content prepackaged foods, the uncertainty of analysis should be controlled in 20%.

Four UV filters, benzophenone-3 (BP-3), 4-methylbenzylidence camphor (4-MBC), ethylhexyl methoxycinnamate (EHMC), and octocrylene (OC), have been examined along the different units of a wastewater reclamation plant (WWRP) located in Tianjin, North China. The analytical procedure included solid-phase extraction and gas chromatographic/mass spectrometric analyses. All four UV filters were detected in the influent during the three sampling campaigns (February, July, and September), and the concentrations ranged from 34 to 2128 ng L(-1). The concentrations of the four UV filters were higher in hot weather (July and September) than in cool weather (February). The monthly average removal ranged from 7.6% to 21% for the selected UV filters during coagulation-flocculation (C-F) treatment. The ozonation treatment achieved the maximum removal (16-28%); on the contrary, the continuous microfiltration (CMF) achieved the lowest removal (3.6-8.2%). The total removal efficiencies along the plant varied from 28% to 43%. These results indicate that the UV filters are not completely removed during WWRP treatment and may be carried over into the environment during the reuse applications.