Chemical Processes Involving 18-Crown-6-Ether in Activated Noncovalent Complexes with Protonated Peptides

These last decades, it has been widely assumed that 18-crown-6-ether (CE) plays a spectator role during the chemical processes occurring in isolated host-guest complexes between peptides or proteins and CE after activation in mass spectrometers. Our present experimental and theoretical results challenge this hypothesis by showing that CE can abstract a proton or a protonated molecule from protonated peptides after activation by collisions in argon or electron capture/transfer. Furthermore, thanks to comparison between experimental and calculated values of collision cross-sections, we demonstrate that CE can change binding site after electron transfer. We also propose detailed mechanisms for these processes.     

Simultaneous Densitometric TLC Analysis of Olmesartan Medoxomil and Hydrochlorothiazide in the Tablet Dosage Form

JPC – Journal of Planar Chromatography – Modern TLC - A simple, rapid, and selective densitometric thin-layer chromatographic (TLC) method has been established and validated for...     

Simultaneous Spectrophotometric Determination of Imipramine Hydrochloride with Chlordiazepoxide and Nortriptyline Hydrochloride with Fluphenazine Hydrochloride

Spectrophotometry was used with multivariate calibration to simultaneously determine compounds in mixtures. Two antidepressant mixtures were investigated: imipramine hydrochloride and chlordiazepoxide and nortriptyline hydrochloride and fluphenazine hydrochloride. Considerable spectral overlap and large differences in component concentrations were challenges. Since this type of analysis is often performed using complex algorithms, a simple strategy was used here for the simultaneous determination of both mixture components by classical least squares, principal component regression, and partial least squares. Experimental design was used to select the optimum parameters including the wavelength range, sampling interval, software, and derivative order. Accuracy was enhanced by proper wavelength selection. In addition, derivatives of the raw spectra improved the selectivity. The standard deviation, deviation of mean recovery from 100%, and prediction ability of the models were used as the responses. In respect to these terms, first-order derivatization of the spectra and a sampling interval of 1?nm provided the best results. In particular, the low concentration compounds in the mixtures (chlordiazepoxide and fluphenazine) were determined more accurately with precision lower than 3%. The strategy was used for the quality control of pharmaceuticals containing the mixtures without chemical pretreatment.     

Chemistry of Phosphorus Ylides. Part 37. The Reaction of Phosphonium Ylides with Indoles and Naphthofurans. Synthesis of Phosphanylidenes,Pyrans, Cyclobutenes,and Pyridazine as Antitumor Agents

The reaction of the stabilized phosphonium ylides 2a , 2b with indolinones 1a , 1b and naphthofuranone 13 afforded the corresponding propylidene and ethylidene derivatives 4a , 4b , 4c , 4d and 14a , 14b . On the other hand, the active phosphacumulenes 5a , 5b react with compounds 4a , 4b , 4c , 4d by [4 + 2]‐cycloaddition to give the stable phosphanylidene indole pyranones 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h . Although compounds 14a , 14b afforded the naphthofuropyrans 16a , 16b , 16c , 16d and triphenylphosphane. Moreover, the phosphallene ylide 7 react with compounds 4a , 4b , 4c , 4d and 14a , 14b to give phosphanylidenecyclobuteneindoline 9a , 9b , 9c , 9d and naphthalenones 18a , 18b , respectively. In addition, the naphthofuropyridazine 21 was obtained from the reaction of the hydrazone 19 and the phosphacumulene 5a . The antitumor activity of some of the new compounds was evaluated, in vitro, against colon and hepatocellular carcinoma cell lines. They showed values closed to that recorded by the reference drug Doxorubicin.     

A comparative study of HPLC-UV and UPLC-DAD methods for simultaneous estimation of aspirin and cilostazol in the presence of their related impurities in bulk and capsules

Aspirin (ASP) and cilostazol (CST) are used as a combination in pharmaceutical formulations for treatment of strokes. Salicylic acid (SAL) is considered to be one of the main synthesis impurities and a degradation product of ASP. On the other hand, the main related impurities of CST are CST related A, B, and C (CST-RA, CST-RB, and CST-RC), respectively. Furthermore, as high efficiency and less elution are the basic requirements of high-speed chromatographic separation, so, a comparative study of two simple, precise, and accurate reversed-phase HPLC and UPLC methods was developed and validated for simultaneous estimation of ASP and CST in bulk and capsules in the presence of SAL, CST-RA, CST-RB, and CST-RC. A Eurospher II C18 (250?×?4.6?mm², 5?µm) for HPLC method and an Agilent Zorbax Eclipse Plus C18 (50?×?2.1?mm², 1.8?µm) for UPLC method were used. A gradient mobile phase of 20?mM anhydrous KH₂PO₄ buffer solution (containing 0.2% triethylamine (TEA), v/v) with pH adjusted to 2.9 using orthophosphoric acid (solution A) and acetonitrile (solution B) mixed in different proportions for HPLC and UPLC methods was prepared. Flow rate was set to 1.0 and 0.3?mL min^?1 for HPLC and UPLC methods, respectively, and the detection was performed for both methods at 210?nm. It worth noting that the proposed UPLC-DAD assay exhibited relatively much more precision, sensitivity, specificity, and economic and chromatographic separation superiority than proposed HPLC-UV assay. Both developed methods were compared with reference methods to prove its applicability and are suitable for purity assessment of ASP and CST in bulk and capsules.     

Entropy, longevity and the cost of annuities

This paper presents an extension of the application of the concept of entropy to annuity costs. Keyfitz (1985) introduced the concept of entropy, and analysed this in the context of continuous changes in life expectancy. He showed that a higher level of entropy indicates that the life expectancy has a greater propensity to respond to a change in the force of mortality than a lower level of entropy. In other words, a high level of entropy means that further reductions in mortality rates would have an impact on measures like life expectancy. In this paper, we apply this to the cost of annuities and show how it allows the sensitivity of the cost of a life annuity contract to changes in longevity to be summarized in a single figure index.     

Antidepressant stimulation of CDP-diacylglycerol synthesis does not require monoamine reuptake inhibition

Background

Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of brain CDP-diacylglycerol synthase - the enzyme that catalyzes the physiological synthesis of CDP-diacylglycerol.

Results

Imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of CDP-diacylglycerol and phosphatidylinositides in PC12 cells. Rat forebrain tissues depleted of serotonin by pretreatment with p-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. With fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. Each drug significantly increased the enzymatic activity of CDP-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues.

Conclusion

Antidepressants probably induce the activity of CDP-diacylglycerol synthase leading to increased production of CDP-diacylglycerol and facilitation of downstream phosphatidylinositol synthesis. Phosphatidylinositol-dependent signaling cascades exert diverse salutary effects in neural cells, including facilitation of BDNF signaling and neurogenesis. Hence, the present findings should strengthen the notion that modulation of brain phosphatidylinositide signaling probably contributes to the molecular mechanism of diverse antidepressant medications.

     

3D graphical representation of protein sequences and their statistical characterization

Based on three physicochemical properties of amino acid side chains, we proposed a novel unique 3D graphical representation of protein sequences. Then, we constructed two vectors of three components as mathematical objects to characterize protein sequences numerically. The similarity/dissimilarity analysis among nine ND5 protein sequences proved the utility of our approach. A correlation and significance analysis have been provided to compare our results and the sequence homology.