Pharmaceutical Chemistry Journal (v.47, #11)

Pharmacokinetic Characteristics of the Radiopharmaceutical “188Re-Albumin Microspheres” After Intravenous Administration to Laboratory Animals by V. M. Petriev; O. V. Siruk; A. A. Bryukhanova; O. A. Smoryzanova; and V. G. Skvortsov (573-576).
Studies of the pharmacokinetics of 188Re-human serum albumin microspheres (MSA) of diameter 10 – 20 μm in intact mice showed that the maximum accumulation of activity (about 70%) 5 min at after intravenous administration was in the lungs. Elimination of activity from the lungs over the period 5 min to 3 h was about 7%. Over a period of 72 h, the quantity of 188Re-MSA in the lungs decreased approximately twofold. Prolonged retention of 188Re-MSA in the lungs could be explained in terms of the high stability of the chemical bond between 188Re and MSA. This was confirmed in control experiments of the pharmacokinetics of free 188Re as Na188ReO4. Results on the pharmacokinetic characteristics of 188Re-MSA provided evidence that this material may be useful for the radionuclide therapy of tumors in different locations after intravascular administration.
Keywords: rhenium-188; radiopharmaceutical; microspheres; pharmacokinetics

Effects of Melaxen and Valdoxan on Superoxide Dismutase and Catalase Activities in Experimental Hyperthyroidism by M. V. Gorbenko; T. N. Popova; K. K. Shul’gin; S. S. Popov (577-580).
The effects of Melaxen and Valdoxan on measures of biochemiluminescence (BCL) were studied on the background of the development of experimental hyperthyroidism in terms of the light sum of chemiluminescence (S) and the maximum peak intensity (I max), which characterize the intensity of free radical processes, and the tangent of the kinetic curve slope (tgα2), which reflects total antioxidant activity; effects on superoxide dismutase and catalase activities in tissues and serum were also studied. Increases in these measures due to oxidative stress in experimental hyperthyroidism were found to normalize in response to these agents.
Keywords: Hyperthyroidism; free radical oxidation; Melaxen; Valdoxan; superoxide dismutase; catalase

The targeted synthesis of biologically active substances in a series of 4-phenyl-5-phenylaminomethyl-1,2,4-triazol-(4H)-3-ylmercaptoacetic acid anilides was planned. Subsequent pharmacological screening was planned using computerized prediction of the potential pharmacological activity. Target products were synthesized by alkylation of key intermediates, i.e., 4-phenyl-5-arylaminomethyl-3-mercapto-1,2,4-triazole-(4H) chloroacetic acid anilides. The structures of the compounds were confirmed by elemental analysis and PMR spectroscopy. Pharmacological screening results identified subjects with high levels of analgesic activity, comparable to that of Analgin, among the study compounds. Compounds had moderate anticonvulsive activity, but less than that of lamotrigine.
Keywords: 1,2,4-triazole derivatives; synthesis; analgesic activity

A QSAR analysis of the anticonvulsive activity of derivatives of five-membered di(tri)azaheterocyclic compounds is presented. Admeworks Model Builder (version 7) was run on Scigress (Fujitsu, Fukuoka, Japan) to calculate 576 descriptors. Regression analysis was performed in which the dependent variable was anticonvulsive activity and the independent variables were the calculated descriptors. This yielded a QSAR model whose accuracy, reliability, and prognostic accuracy were confirmed by statistical tests. Anticonvulsive activity of these substances was found to depend on 3D descriptors - PCHGNH and PCHGNS - and 2D autocorrelational descriptors - GATS7v, GATS3e, and MARS3m.
Keywords: Correlations; descriptors; anticonvulsive activity; derivatives of five-membered di(tri)-azaheterocyclic rings

Synthesis and Antifungal Activity of Substituted Nitrotetrazole-5-Carbaldehyde Hydrazones by A. G. Tyrkov; M. A. Abdel’rakhim; L. T. Sukhenko; O. V. Degtyarev (589-592).
A series of nitrotetrazole-5-carbaldehyde hydrazones was synthesized and their antifungal activity against Candida albicans, Microsporum canis, and Trichophyton rubrum was assessed.
Keywords: synthesis; nitrotetrazole-5-carbaldehyde hydrazones; antifungal activity

Thermolysis of 5-aryl-4-quinoxalin-2-ylfuran-2,3-diones yielded 6-aryl-9-(3-aryl-2-quinoxalinyl)-7-aroyl-10-oxo-10H-pyrido[1,2-a]quinoxalin-8-yl arylates, alkaline hydrolysis of which produced 6-aryl-9-(3-aryl-2-quinoxalinyl)-7-aroyl-8-hydroxy-10H-pyrido[1,2-a]quinoxalin-10-ones. The compounds synthesized here had analgesic activity.
Keywords: analgesic activity; 6-aryl-9-(3-aryl-2-quinoxalinyl)-7-aroyl-10-oxo-10H-pyrido[1,2-a]quinoxalin-8-yl arylates; 6-aryl-9-(3-aryl-2-quinoxalinyl)-7-aroyl-8-hydroxy-10H-pyrido[1,2-a]quinoxalin-10-ones

Studies of Nitrate Accumulation in Fresh Echinacea Purpurea Herb and Its Processed Products by V. B. Zagumennikov; A. V. Molchanova; E. Yu. Babaeva; A. L. Petrova (596-598).
The accumulation of nitrates in fresh Echinacea purpurea herb grown in the conditions of the non-chernozem zone of the Russian F ederation in 2009 – 2010 were studied in its constituent parts, the juice, and the pulp, in relation to plant age (2, 3, 4, 5, and 7 years of growth) and year of analysis. The greatest accumulation of nitrates in the plant was seen in the stems. The highest nitrate content was seen in the juice, where levels were 1.4 – 2.7 times higher than in the medicinal plant raw material.
Keywords: nitrates; Echinacea purpurea fresh herb; juice

Biologically Active Compounds from Lemna Minor S. F. Gray by I. N. Vladimirova; V. A. Georgiyants (599-601).
The chemical composition of biologically active compounds of the common duckweed (Lemna minor) was studied. A titrimetric method was used to assay the total iodine content, a spectrophotometric method was used for flavonoids, expressed as luteolin-7-glucoside; gas chromatography/mass spectrometry was used to identify 32 lipophilic substances of various chemical groups. Atomic emission spectrographic studies identified 14 macro and trace elements in the common duckweed. Studies of biologically active substances in the common duckweed are of interest for further investigation of its pharmacological properties with the aim of seeking new medicinal agents.
Keywords: Lemna minor S. F. Gray; macro and trace elements; iodine; flavonoids; lipophilic compounds

HPLC with mass spectroscopic detection was used to demonstrate that Forsythia intermedia (Forsythia x intermedia Zabel) flowers contain flavolignans: forsythin, phillygenin, isolariciresinol and, presumptively, its derivative hydroxyisolariciresinol, as well as the phenylethanoid glycoside forsythoside A. Forsythoside A was assayed by two methods - HPLC with spectrophotometric detection and capillary electrophoresis. Forsythoside A contents in flowers reached 1.5%.
Keywords: Forsythia intermedia ; flavolignans; forsythoside A; capillary electrophoresis; HPLC/MS

Studies of the Hydrolysis of Hesperidin by O. S. Evseeva; O. A. Andreeva; É. T. Oganesyan (606-609).
A variety of hydrolytic mixtures for the cleavage of glycoside bonds in hesperidin was studied. The optimum system for complete hydrolysis of hesperidin to prepare the aglycone consisted of CH3COOH, H2SO4, and C2H5OH at a ratio of 1:1:9. Studies of the kinetics of the hesperidin hydrolysis reaction in this system showed that the process was a first-order reaction, as demonstrated by the constant k. The maximum aglycone yield over time, 98%, was obtained by boiling the reaction mix for 8.5 h. This confirmed the suitability of our model. Prepared of hesperidin-7-O-glucoside should be by fractional hydrolysis in a system consisting of CH3COOH, H2SO4, and C2H5OH at a ratio of 1:1:9.
Keywords: hydrolysis; hesperidin

The kinetics of the production of paracetamol and oxaphenamide in the single-stage reductive acylation of p-nitrophenol on palladium-containing anionites in mild conditions were studied. Metal-polymer complexes were found to have high activity and selectivity. Target product yields were 48 – 90%.
Keywords: reductive acylation; paracetamol; oxaphenamide; catalysis

Studies of the Solubility of Rutin from Solid Dispersions by I. V. Koval’skii; I. I. Krasnyuk; I. I. Krasnyuk Jr.; O. I. Nikulina; A. V. Belyatskaya; Yu. Ya. Kharitonov; N. B. Fel’dman; S. V. Lutsenko; V. V. Grikh (612-615).
The effects of solid dispersions (SD) on the solubility of rutin were studied. Rutin and its SD with polyethylene glycol 1500 and polyvinylpyrrolidone 10000 were studied. Preparation of SD increased the solubility and rate of dissolution of the active substance. The solubility of rutin from SD increased by a factor of 52. The physicochemical methods used here suggested that improvements in rutin release from SD result from decreases in crystallinity and formation of solid solutions of drug in polymer.
Keywords: solid dispersions; solubility; antioxidant; rutin; polyethylene glycol 1500; polyvinylpyrrolidone 10000

A Thermoanalytic Method for the Analysis of Biologically Active Substances using Isobornylphenol Derivatives as an Example by O. N. Nikulicheva; A. P. Krysin; V. P. Fadeeva; E. A. Krasnov; E. E. Nazmutdinova (616-619).
Data on the thermal degradation of isobornylphenols (IBP) are presented, along with the kinetic characteristics of the thermolysis of these compounds, which were compared with values calculated from previously studied biologically active compounds belonging to the same class of spatially hindered phenols (SHP). The relationship between the activation energy and the pre-exponential factor identifies similarities in the mechanisms of degradation of IBP and previously studied SHP.
Keywords: thermal analysis; biologically active compounds; kinetic characteristics; isobornylphenols; spatially hindered phenols

Analysis and Standardization of Levofloxacin Substance by M. K. Sedova; M. S. Sergeeva; M. E. Dudenkova; L. M. Gaevaya; L. N. Grushevskaya; N. I. Avdyunina; B. M. Pyatin (620-626).
Amethod for the analysis and standardization of levofloxacin substance synthesized using an original method was developed. The physicochemical properties of batch samples of levofloxacin substance were studied; IR and UV spectra were recorded for identification; contents of contaminants and R-ofloxacin in substance were determined by HPLC; residual solvent contents were determined by GLC. Samples of substance were assayed by HPLC. The shelf life was determined and quality norms were specified for levofloxacin substance; the results were used to prepare a draft pharmacopoeia monograph for levofloxacin substance.
Keywords: levofloxacin; substance; analysis; standardization; high-performance liquid chromatography; HPLC; contaminants; R-ofloxacin; residual solvents; gas-liquid chromatography; GLC