Synthesis and cytotoxicity of new 2-oxo-7-phenyl-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid amides

Abstract

The synthesis and anticancer activity evaluation of new thiazolo[4,5-b]pyridine-5-carboxylic acid amides is described. The structures of the synthesized compounds were confirmed by spectroscopic data and a single crystal X-ray diffraction analysis for 2.4. The synthesized compounds were screened for their in vitro anticancer activity according to US NCI protocols. The most active 7-(4-fluorophenyl)-2-oxo-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid (4-chlorophenyl)amide 2.2 and 7-(4-chlorophenyl)-2-oxo-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid (4-chlorophenyl)amide 2.5 were screened for their cytotoxicity effects on C6 Rat glioma cells and U373 Human glioblastoma astrocytoma cells which revealed promising results comparable to temozolamide as reference control according MTT assay data.     

Facile Oxidative Rearrangements Using Hypervalent Iodine Reagents

Aromatic substituents migrate in a novel oxidative cyclization mediated by iodine(III) reagents. 4-Arylbut-3-enoic acids are cyclized and rearranged to 4-arylfuran-2(5H)-ones by hypervalent iodine compounds in good to excellent yields under mild reaction conditions. Other ring sizes are also accessible. The mechanism of the reaction is described in detail, and calculations highlight the cationic nature of the intermediates in the rearrangement. The fast access to heavily substituted furanones is used for the synthesis of biologically active derivatives.     

Influence of amidoammonium calix[4]resorcinarenes on methyl orange protolytic equilibrium: supramolecular indicator systems

Here, we report on the study of cationic amidoammonium calix[4]resorcinarenes 1–5 of various lipophilicity capable of binding acid–base indicator methyl orange (MO). We identified the contributions of macrocycle aggregation and conformational mobility in the binding of MO. The effective pK_a values of bound MO systematically decrease as the size and the packing density of the aggregates increase with an increase in calixresorcinarene lipophilicity. Consideration of a series of macrocycles clearly shows that large aggregates form most stable complexes, binding guests not on individual level but as aggregates. It was found that the most stable MO complex with 5 is formed due to electrostatic binding with ammonium groups of the macrocycle and incapsulation of MO in a hydrophobic layer of the aggregates. We have shown that competitive binding of MO and cationic surfactants by aggregates of 5 is suitable for visual/spectrophotometric detection of colourless anionic substrates.     

Quality assurance in immunoassay performance—comparison of different enzyme immunoassays for the determination of caffeine in consumer products

Enzyme immunoassays with optical detection are amongst the most widely used bioanalytical tools. We defined seven parameters for the quality assessment of immunoassays that were addressed in a systematic study of direct and indirect immunoassays, using the enzymes horseradish peroxidase (HRP) and alkaline phosphatase (AP), the chromogenic substrates 3,3′,5,5′-tetramethylbenzidine (TMB) and para-nitrophenyl phosphate, and the fluorescent substrates 3-(4-hydroxyphenyl)propionic acid and 4-methylumbelliferyl phosphate. The same monoclonal antibody against caffeine was used throughout the study. The four quality parameters regarding the standard curve were the test midpoint (sensitivity), the measurement range, the relative dynamic range of the signal, and the goodness of fit of the adjusted four-parameter logistic function. All HRP immunoassays showed a higher sensitivity compared to the AP assays. On the basis of all four criteria, it was established that the direct assay format is superior to the indirect format, the immunoassay using HRP TMB fulfilling all requirements best. In a second step, caffeine concentrations in 24 beverage and cosmetics samples were determined and three more quality parameters were assessed with this application. The direct HRP TMB assay showed one of the best intra- and inter-plate precisions and the best accuracy, defined by the correlation of results with those from the chosen reference method liquid chromatography tandem mass spectrometry (LC-MS/MS). Considering all criteria, HRP TMB seems to be the enzyme substrate system of choice preferably used in the direct assay format.

Identification and functional characterization of a novel α-conotoxin (EIIA) from Conus ermineus

Nicotinic acetylcholine receptors (nAChRs) are one of the most important families in the ligand-gated ion channel superfamily due to their involvement in primordial brain functions and in several neurodegenerative pathologies. The discovery of new ligands which can bind with high affinity and selectivity to nAChR subtypes is of prime interest in order to study these receptors and to potentially discover new drugs for treating various pathologies. Predatory cone snails of the genus Conus hunt their prey using venoms containing a large number of small, highly structured peptides called conotoxins. Conotoxins are classified in different structural families and target a large panel of receptors and ion channels. Interestingly, nAChRs represent the only subgroup for which Conus has developed seven distinct families of conotoxins. Conus venoms have thus received much attention as they could represent a potential source of selective ligands of nAChR subtypes. We describe the mass spectrometric-based approaches which led to the discovery of a novel α-conotoxin targeting muscular nAChR from the venom of Conus ermineus. The presence of several posttranslational modifications complicated the N-terminal sequencing. To discriminate between the different possible sequences, analogs with variable N-terminus were synthesized and fragmented by MS/MS. Understanding the fragmentation pathways in the low m/z range appeared crucial to determine the right sequence. The biological activity of this novel α-conotoxin (α-EIIA) that belongs to the unusual α4/4 subfamily was determined by binding experiments. The results revealed not only its selectivity for the muscular nAChR, but also a clear discrimination between the two binding sites described for this receptor.     

Novel combination of non-aqueous capillary electrophoresis and multivariate curve resolution-alternating least squares to determine phenolic acids in virgin olive oil

This paper presents the development of a non-aqueous capillary electrophoresis method coupled to UV detection combined with multivariate curve resolution-alternating least-squares (MCR-ALS) to carry out the resolution and quantitation of a mixture of six phenolic acids in virgin olive oil samples. p-Coumaric, caffeic, ferulic, 3,4-dihydroxyphenylacetic, vanillic and 4-hydroxyphenilacetic acids have been the analytes under study. All of them present different absorption spectra and overlapped time profiles with the olive oil matrix interferences and between them. The modeling strategy involves the building of a single MCR-ALS model composed of matrices augmented in the temporal mode, namely spectra remain invariant while time profiles may change from sample to sample. So MCR-ALS was used to cope with the coeluting interferences, on accounting the second order advantage inherent to this algorithm which, in addition, is able to handle data sets deviating from trilinearity, like the data herein analyzed. The method was firstly applied to resolve standard mixtures of the analytes randomly prepared in 1-propanol and, secondly, in real virgin olive oil samples, getting recovery values near to 100% in all cases. The importance and novelty of this methodology relies on the combination of non-aqueous capillary electrophoresis second-order data and MCR-ALS algorithm which allows performing the resolution of these compounds simplifying the previous sample pretreatment stages.     

The 3-Methyl-1,3-butadienyl Phenyl Sulfoxide I. Preparation and Some Properties

The title sulfoxide 5 is worthy of interest because of its isoprenoid structure and its synthetic potentialities¹