Vol 52, No 3 (2018)

The effect of the synthetic biguanide derivative N-[imino(1-piperidinyl)methyl]guanidine on free-radical processes, diene conjugate levels, and superoxide-dismutase and catalase activity in kidneys of rats with experimental type 2 diabetes mellitus (DM2) was studied. It was established that administration of this compound to rats with DM2 helped to normalize the studied parameters, which may have been due to its positive regulating effect on free-radical homeostasis.

Issues pertaining to determination of the pharmacokinetic parameters of calcium preparations are examined using their comparative bioavailability as an example. Pharmacokinetic parameters of calcium such as area under the concentration—time curve (AUC) and maximum concentration (C_max) are calculated considering the background calcium contents in volunteers. Calcium excretion with urine is assessed as clearance of creatinine, a calcium elimination factor. The dynamics of the content of parathormone (PTH), the main hormone regulating calcium homeostasis, are studied. The results can be used to plan clinical trials for assessing the pharmacokinetics of drug analogs of endogenous compounds.

A series of previously undescribed N-aryl-N′-pyridin-2-ylureas were prepared via the reaction of 2-aminopyridines with benzoyl azides and tested in vitro as activators of glucokinase. Statistically significant reductions of glucose levels as compared with controls were demonstrated for several compounds.

The effects of different initial processing methods on the amount of gastrodin and gastrodigenin isolated from Gastrodia elata Blume were investigated and the best initial processing technology was optimized. The contents of gastrodin and gastrodigenin were analyzed by high performance liquid chromatography (HPLC). It is established that G. elata boiling in water followed by ethanol extraction is the best initial processing technology, which can provide the basis and reference for the standardized processing of G. elata herbs.

The solubility and stability of the nonselective α-adrenoblocker 1-(2,3-dihydro-1,4-benzdioxin-6-yl)-3-(3-phenyl-1-pyrrolidinyl)-1-propanone hydrochloride (proroxan) at various pH values were investigated. It was established that proroxan solubility was reduced for 3 < pH < 5.5, which corresponded to the protonated species; was uncharacteristic for salts of organic bases; and increased its destruction. It was suggested that this peculiarity of proroxan behavior in aqueous solutions could reflect complexation between its protonated and unprotonated molecules. The results indicated that proroxan preparations using dosage forms and delivery systems that provide its maximum absorption in the stomach must be developed.

An HPLC-MS/MS method for quantitative determination of the new antituberculosis drug PBTZ169 in blood serum, urine, and feces using perindopril as an internal standard was developed and validated. The method was selective, specific, accurate, and precise. Calibration curves were linear in the ranges 2 – 2,000, 5 – 3,000, and 100 – 10,000 ng/mL for blood serum, urine, and feces, respectively, with correlation coefficients >0.99. The detection limits of PBTZ169 were 1, 2.5, and 50 ng/mL for serum, urine, and feces, respectively. The limits of quantitation were 2 ng/mL in serum; 5, urine; and 100, feces.

In this study, magnetic nanoparticles were functionalized with dextran and immobilized ibuprofen, diclofenac, and dopamine in order to investigate the diffusion of drugs through a dialysis membrane under biological conditions such as a temperature of 37.0°C and pH 7.4. The concentration of released drugs was measured both inside the membrane and upon release into solution using spectrofluorimetric and spectrophotometric methods. The mechanism of drug release from the carrier was analyzed in terms of the Korsmeyer – Peppas model. The results show that differences in the mechanism of drug release depend on the time-diffusion process and the type of drug used. In addition, the atomic force microscopy and confocal microscopy methods were used to investigate the interaction between bacterial cells and functionalized nanoparticles.

Diethylcarbamazine citrate (DEC) is a piperazine anthelmintic agent indicated for the treatment of individual patients with lymphatic filariasis. Two simple and sensitive UV-spectrophotometric techniques have been developed and validated for the determination of this drug in bulk parent substance and tablets, based on the measurement of the absorbance of DEC solution either in 0.1M HCl at 210 nm (method A) or in 0.1M H₂SO₄ at 209 nm (method B). Beer’s law was obeyed over the concentration ranges of 1.25 – 25.0 and 2.5 – 30.0 μg · mL^-1, for method Aand method B, respectively, and the corresponding molar absorptivity values were 2.02 × 10⁴ and 1.21 × 10⁴ L mol^-1 · cm^-1. The limits of detection (LOD) and quantification (LOQ) were, respectively, 0.26 and 0.78 μg · mL^-1 (method A), and 0.16 and 0.49 μg · mL^-1 (method B). These methods were assessed for intra-day and inter-day accuracy and precision, as well as robustness and ruggedness. Both methods were applied to one brand of tablets with percentage label claim of 101.7 and 100.8 for method A and method B, respectively, and the standard deviation was below 2%. In order to establish the stability-indicating ability of these methods, the drug was analyzed after subjecting it to acid and base hydrolysis, oxidation, heat and light stress conditions and the results indicated that the drug degraded extensively under both base- and oxidative-stress conditions, and remained intact under other stress conditions.

The production of lovastatin by Aspergillus terreus PU-PCSIR-1 was studied using submerged fermentation technique. Effects of pH, incubation temperature, incubation time, and the media components on the production of lovastatin were investigated. Maximum lovastatin yield (198.90 mg/L) was achieved after 14 days of incubation at temperature 28°C and pH 7.4. Peptonized milk, linoleic acid, glucose, yeast extract, and trace elements had a positive impact on the production of lovastatin by A. terreus.

A series of new 2-aminopyrrole derivatives [2-amino-1-aryl-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamides IIa-h] were synthesized via the reaction of 4-arylamino-2-tert-butyl-2,5-dihydro-5-oxofuran-2-ylacetates (Ia-h) with 2-cyano-N-(thiazol-2-yl)acetamide in the presence of Et₃N. Studies of the biological activity of the synthesized compounds found that they possessed low toxicity and that 2-amino-1-(2-bromophenyl)-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamide (IIb) and 2-amino-1-(2,4-dichlorophenyl)-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-N-(thiazol-5-yl)-4,5-dihydro-1H-pyrrole-3-carboxamide (IIg) exhibited radical-binding activity greater than that of trolox and cytotoxic activity against gastrointestinal stromal tumor (GIST) cells, including those resistant to the target drug imatinib (Glivec). The cytotoxic activity of the synthesized compounds was comparable with that of doxorubicin chemotherapeutics and exceeded significantly those of etoposide, paclitaxel, and hydroxyurea. Apossible molecular mechanism of action of the synthesized compounds might be their ability to disrupt cell division and induce selective accumulation of M-phase cells with subsequent death by a mitotic catastrophe pathway.

The preparation of Solidago caucasica herbal dry extract from the plant was studied by us for the first time. The main quality indicator was a flavonoid content of ≥ 2.5%. Other biologically active compounds, e.g., coumarins, phenolic carboxylic acids, and organic acids, were also present.

The scientific and technical literature addressing the synthesis of anisotropic iron-oxide nanoparticles of various shapes (cubic, rod-like, clustered, etc.) sized from 10 to 100 nm and their application for diagnostic magnetic resonance imaging (MRI) of tissues and organs is analyzed. The analysis indicates that the nanoparticle shape, size, and surface chemistry affect considerably relaxation parameters T₁ and T₂. Thus, cubic iron-oxide nanoparticles had the greatest T₂ values. Furthermore, rod-like and octapodal nanoparticles also exhibit rather high T₂ values so that they can be used as contrast agents for diagnostic MRI.

Experimental data on the comparative dissolution kinetics of two ibuprofen preparations from different manufacturers are presented. The study was performed in three buffer solutions at pH 1.2, 4.5, and 6.8 according to requirements of the Scientific Center for Expert Evaluation of Medicinal Products of the Russian Federation. A fourth dissolution medium was buffer solution at pH 7.2, which is included in a draft regulation. The test used a Erweka DT-720 rotating-basket device.