Indium mediated allylation in peptide and protein functionalization

Indium-mediated allylation has been used in the site-selective functionalization of N-terminal aldehydes of peptides and proteins. This is the first demonstration of indium-mediated C-C bond formation in protein labelling studies under mild and environmentally friendly conditions.     

Identification of new novel scaffold for Aurora A inhibition by pharmacophore modeling and virtual screening

Aurora kinases belong to family of highly conserved serine/threonine protein kinases that are involved in diverse cell cycle events and play a major role in regulation of cell division. Abnormal expression of Aurora kinases may lead to cancer; hence, these are considered as a potential target in cancer treatment. In this research article, we identified three novel Aurora A inhibitors using modern computational tools. A four-point common 3D pharmacophore hypothesis of Aurora A (AurA) inhibitors was developed using a diverse set of 55 thienopyrimidine derivatives. A three-dimensional quantitative structure–activity relationship (3D-QSAR) study was carried out using atom-based alignment of diverse set of 55 molecules to evaluate the structure– activity relationships. Docking and 3D-QSAR studies were performed with the 3D structure of AurA to evaluate the generated pharmacophore. The pharmacophore model and 3D-QSAR results complemented the results of our docking study. The pharmacophore hypothesis, which yields the best results, was used to screen the Zinc ‘clean drug-like’ database. Various database filters such as 3D-arrangement of pharmacophoric features, predicted activity and binding interaction score were used to retrieve hits having potential AurA inhibition activity.     

A novel （G＇/G）-expansion method and its application to the Boussinesq equation

In this article, a novel （G＇/G）-expansion method is proposed to search for the traveling wave solutions of nonlinear evolution equations. We construct abundant traveling wave solutions involving parameters to the Boussinesq equation by means of the suggested method. The performance of the method is reliable and useful, and gives more general exact solutions than the existing methods. The new （G＇/G）-expansion method provides not only more general forms of solutions but also cuspon, peakon, soliton, and periodic waves.     

Cloud Point Phenomenon in Amphiphilic Drug Promethazine Hydrochloride+Electrolyte Systems

Herein we report clouding phenomenon occurring in amphiphilic drug promethazine hydrochloride (PMT) in the presence of electrolytes. The CP of 50 mM drug solution, prepared in 10 mM sodium phosphate buffer, was found to decrease with increasing pH due to deprotonation of drug molecules at high pH. Addition of inorganic salts (KF, KCl and KBr) to drug solutions at fixed pH (6.7) and drug concentration (50 mM) caused an increase in CP. The results have been discussed on the desorption/adsorption of counterions to the headgroups. Cations also increased the CP by affecting the water structure with their effectiveness being in the order: Li⁺<Na⁺<K⁺<NH₄ ⁺. In the presence of NaCl, increase in drug concentration increased the CP while increase in pH showed an opposite trend.     

Development and Characterization of Liposome‐Based Formulation of Amiloride Hydrochloride

Amiloride hydrochloride, a generally used diuretic recently has been found effective in the treatment of epilepsy. The side effects of the drug, such as hyperkalemia, hypertension, and hyperaldosteronism were controlled by reducing the dose and targeting the drug to the brain. The objective of this study was to determine the factors influencing encapsulation of amiloride hydrochloride in liposomes and to demonstrate the anti‐epileptic potential of liposomal drug. A series of liposomal formulations of amiloride hydrochloride were prepared by varying the compositions of the formulations. The optimized formulation consisted of 10 mg/mL of amiloride hydrochloride, L‐phosphatidyl choline, lecithin, cholesterol, and butylated hydroxy toulene. The percentage entrapment efficiency in the optimized formulation was 44%. The drug to lipids ratio and L‐phosphatidyl choline: lecithin: cholesterol: butylated hydroxy toulene ratios were 2.0:3.0 and 5:5:5:2, respectively. The formulation showed an in vitro release of 98.17% in 8 hours, and the best fit kinetic model was Peppas model. Treatment with amiloride hydrochloride liposomes resulted in a significant increase in seizure threshold as compared to free drug in increasing current electroshock seizures in mice, which indicated an increase in CNS uptake of drug in liposome formulation.     

Investigation on the Adsorption and Corrosion Inhibition Behavior of Gum Acacia and Synergistic Surfactants Additives on Mild Steel in 0.1 M H2SO4

Adsorption and corrosion inhibition effect of gum acacia alone and in presence of surfactants sodium dodecyl benzene sulphonate and cetyltrimethyl ammonium bromide on mild steel in 0.1 M H₂SO₄ in temperature range of 30 to 60°C was investigated using weight loss method, chemical analysis of solution, scanning electron microscopy, atomic force microscopy and determination of thermodynamic parameters. Inhibiting action of gum acacia is synergistically enhanced on addition of small amount of surfactants. SEM and AFM results confirmed the existence of an adsorbed protective film on the mild steel surface. Thermodynamic parameters reveal that adsorption process is spontaneous and obey Freundlich adsorption isotherm.     

Synthesis and Blood Glucose Lowering Activity of Novel Benzenesulfonyl-Urea Derivatives

Treatment of the pyridazinone derivatives ( 1a, 1b ) with ethyl chloroformate afforded novel carbamates ( 2a, 2b ). Subsequent treatment of 2a, 2b with appropriate amines gave novel benzenesulfonylurea derivatives ( 3a–i ). All these compounds were characterized on the basis of ¹ H NMR, IR, Mass spectral data and elemental analysis results. Preliminary biological testing of urea derivatives revealed that some compounds possess significant blood sugar lowering activity. Four compounds ( 3c, 3f, 3g , and 3h ) were found to have promising blood glucose lowering activity and may be used as lead compounds for developing new antidiabetic drugs.     

Internet resources in GPCR modelling1

G-Protein coupled receptors (GPCRs), one of the most important families of drug targets, belong to the super family of integral membrane proteins characterized by seven transmembrane helices. Because they are difficult to crystallize, the three dimensional structure of these receptors have not yet been determined by X-ray crystallography, except one. In the absence of a 3-D structure, in-silico approaches for solving the structure of this class of proteins are widely used and provide valuable information for structure based drug design. There are several web servers and computer programs available that automate the modelling process of GPCRs. Some of these include Modeller, Swiss-Model server, Homer, etc. Using these tools reliable homology models of human histamine H1 receptor (HRH1) and thrombin receptor (PAR-1) have been generated which explain the binding mode of the standard antagonists of these receptors and may be useful in designing their novel antagonists.     

OPTIMIZATION OF THE SYNTHESIS OF ACRYLAMIDE HYDROGEL BY γ-RAY IRRADIATION

Hydrogels have been synthesized from 10%, 20%, 30%, 40%, 50% and 60% aqueous solutions of acrylamide monomer by gamma radiation employing doses in the range of 0.2-30 kGy from a Co-60 source. The effect of solution concentration, γ-ray dose, pH and time was studied in order to observe the optimizing conditions in the characterization of hydrogels. Gel fraction increases with dose for all concentrations indicating hundred-percentage conversion of gel at doses ≥5 kGy for homogenous solutions in the range of 20%-50% concentration. On the other hand, 10% solution provides conversion less than 86% even at 30 kGy, whereas 60% monomer makes an inhomogeneous solution which stile gives about 100% gel fraction. Swelling of hydrogels under water with respect to time varies with both the doses and concentrations due to the change of crosslinking density in the gels. The maximum volume change of hydrogels during swelling and water desorption mainly occurs within 24 h. Swelling is also enhanced with the rise of pH due to change of ionic content of the solvent. Considering the amount of gel fraction and the properties of hydrogel, the samples prepared from 20% solution at 5kGy show better results. Moreover, the effect of bacteria on hydrogel was found to be nil, suggesting a prohibition of growth of microorganism in it.