Validated Stability-Indicating Method for Alendronate Sodium Employing Zwitterionic Hydrophilic Interaction Chromatography Coupled with Charged Aerosol Detection

Alendronate sodium is widely used in the treatment of osteoporosis and Paget’s disease. The HPLC method development for alendronate sodium, in particular, is challenging owing to the absence of chromophoric group and its high polarity. In the present study, a short and simple isocratic method was developed involving hydrophilic interaction liquid chromatography, coupled with a charged aerosol detector. The developed method was validated according to the ICH Q2(R1) guideline and was successfully applied for the analysis of a marketed formulation containing the drug.

     

Molecular activities and ligand-binding specificities of StAR-related lipid transfer domains: exploring integrated in silico methods and ensemble-docking approaches

In this study, cholesterol biotransformation gene-set of human steroidogenic acute regulatory protein-related lipid transfer (START) domains were evaluated from high-throughput gene screening approaches. It was shown that STARD1, STARD3 and STARD4 proteins are better effective transporters of cholesterol than STARD5 and STARD6 domains. Docking studies show a strong agreement with gene ontology enrichment data. According to both complementary strategies, it was found that only STARD1, STARD3 and STARD4 are potentially involved in cholesterol biotransformation in mitochondria through Ω1-loop of C-terminal α4-helical domain. Ensemble docking assessment for a set of selected chemicals of protein–chemical networks has shown possible binding probabilities with START domains. Among those, reproductive toxicity evoked drugs (mifepristone), insecticides (rotenone), tobacco pulmonary carcinogens (benzo(a)pyrene) and endocrine disruptor chemicals (EDCs) including perfluorooctanesulfonic acid (PFOS) and aflatoxin B₁ (AFB₁) potentially bound with novel hotspot residues of the α4-helical domain. Compound representation space and clustering approaches reveal that the START proteins show more sensitivity with these lead scaffolds, so they could provide probable barrier assets in cholesterol and steroidogenic acute regulatory (StAR) binding and leads adverse consequences in steroidogenesis. These findings indicate potential START domains and their binding levels with toxic chemicals; sorted viewpoints could be useful as a promising way to identify chemicals with related steroidogenisis impacts on human health.     

Synthesis of some N-[pyridyl(phenyl)carbonylamino]hydroxyalkyl-(benzyl)-1,2,3,6-tetrahydropyridines as potential anti-inflammatory agents

1,2,3,6-Tetrahydropyridines are known to possess analgesic, anti-inflammatory, hyperglycemic and hypoglycemic activities. Substituted 2,4-dinitrophenylpyridinium chlorides 3 were formed by reacting 1-chloro-2,4-dinitrobenzene with hydroxypropyl, hydroxymethyl and benzyl substituted pyridines 2 . Attack of the pyridinium chlorides 3 with pyridylcarbonyl hydrazides or benzoyl hydrazides 4 gave the isolable 2,4-dinitroanilino derivative 5 which underwent hydrolysis when refluxed in water:p-dioxane mixture (1:4 v/v) to afford the pyridinium ylides 6 . Sodium borohydride reduction of 6 in absolute ethanol at 0° for 4–6 hours resulted in the isolation of the 1,2,3,6-tetrahydropyridines 7 in good yields.     

Synthesis of some N-[pyridyl(phenyl)carbonylamino]-alkyl-1,2,3,6-tetrahydropyridines

Alkyl substituted 2,4-dinitrophenylpyridinium chlorides 3 are formed by the nucleophilic substitution of 1-chloro-2,4-dinitrobenzene with alkyl pyridines. Reaction of pyridyl acid hydrazides or benzoyl hydrazides 4 with the pyridinium chlorides 3 furnish the isolable 2,4-dinitroanilino derivatives 5 which undergo hydrolysis when refluxed in water:p-dioxane mixture (1:4 v/v) to yield the pyridinium ylides 6 . Sodium borohydride reduction of 6 in absolute ethanol at 0° for 4 hours result the formation of the title compounds 7 in moderate to excellent yields.     

Beitrag zur Klärung des Grossen Flusswiderstandes von Selengleichrichtern

The differential resistance of selenium rectifiers in the linear part of the V–I characteristic in the forward direction is considered; its value is three orders of magnitude higher than that of monocrystalline Ge-or Si-rectifiers and is closely connected with the current carrying capacity of selenium rectifiers. X-ray pictures showing the crystalline structure of selenium layers after heat treatment of different duration show increasing crystal growth in the polycrystalline selenium layer so that the differential resistance should be reduced. Measurement of the differential resistance, however, showed a gradual increase following an initial decrease, which is obviously connected with the process of ageing.