Vol 50, No 8 (2016)

A series of novel pyrrolo[1,2-a]pyrazines that were ligands of 18 kDa translocator protein (TSPO) were synthesized at Zakusov SIP. The compounds N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-1) and N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3) were found to possess high TSPO affinity and pronounced anxiolytic activity. The anxiolytic effects of GML-1 and GML-3 in elevated plus-maze tests were completely blocked by the neurosteroidogenic-enzyme inhibitors trilostane and finasteride.

The rate of free-radical oxidation in rat heart with experimental hyperthyroidism (EH) was estimated after Melaxen and Valdoxan administration. It was found that the content of protein carbonyl groups increased if the pathology developed in cardiomyocytes. This indicated that they were oxidized. Increased concentrations of primary lipid peroxidation products (diene conjugates), inhibition of aconitate hydratase activity, and accumulation of citrate were noted. Injection of Melaxen and Valdoxan to rats with EH normalized these parameters. The melatonin-correcting capability of the used drugs and the antioxidant activity of melatonin probably facilitated normalization of free-radical homeostasis in rat cardiomyocytes with the pathology.

A series of methyl 3-acyl-6-amino-4-aryl-5-cyano-4H-pyran-2-carboxylates were synthesized using the reaction of methyl 2,4-dioxobutanoates with arylidenemalononitriles in EtOAc in the presence of catalytic amounts of morpholine or piperidine. The structures of the compounds were elucidated using IR, PMR, ¹³C NMR, and mass spectral data. The antimicrobial, analgesic, and antipyretic activities of the synthesized compounds and their influence on antibody response were studied.

A series of 4-(4-dimethylaminophenyl)pyridine derivatives were synthesized and tested for antimicrobial activity. 4-(4-Dimethylaminophenyl)-1-phenacylpyridinium bromide and 4-(4-dimethylaminophenyl)-1-dimethylcarbamoylpyridinium chloride were highly active against M. luteum and C. tenuis test cultures.

2-Thiocyanato-(2-methyl)-3-[4-(3-)-thiocyanatophenyl]propionamides exhibited rather high antimicrobial activity with respect to staphylococci, E. coli, yeast-like fungi, and pseudomonas that was practically absent in bis-thiocyanatoamides of benzidine and its derivatives.

Microencapsulated vinpocetine was produced by liquid—liquid dispersion using a mixture of beeswax and cocoa oil in a 3:2 ratio as the carrier. The dispersion media were purified H₂O and sodium carboxymethylcellulose (Na-CMC) solution (2%). Drug release from the microcapsules was studied in vitro as a function of microcapsule size, shell material, and dispersion medium. The best characteristics were observed for microcapsules with a hydrophobic coating containing beeswax and cocoa oil in a 3:2 ratio of size 0.5 – 1 mm that were produced in Na-CMC solution (2%).

Traditional Chinese medicinal plant Paeonia veitchii Lynch. has a complicated chemical composition. For profound study of the medicinal value of Paeonia genus, systematic chromatographic investigations were carried out on n-butyl alcohol fractions of the ethanol extract for the separation of monoterpene glycoside compounds. Six compounds were isolated from the extract, which were identified on the basis of spectral analysis and physicochemical evidence. They are paeoniflorin (1), 4-O-methyloxypaeoniflorin (2), 4-O-methylpaeoniflorin (3), 4-O-ethylpaeoniflorin (4), paeonidanin (5), and 9-ethyl-neo-paeoniaflorin A (6). Compounds 2, 3, and 5 were isolated from this plant for the first time.

A series of six new 2-[7-(fluorobenzyloxy)-4-oxo-4H-chromen-3-yl]-1-hydroxyimidazoles were synthesized and characterized as potential HIV-1 integrase inhibitors. Prototropic tautomerism of the obtained 1-hydroxyimidazoles was discussed. Their ability to inhibit integrase catalytic activity in 3′-terminal processing and chain transfer reactions was studied. It was shown that these compounds did not exhibit noticeable inhibition.

Results from technology development for manufacturing an amben prolonged-release preparation based on a Kollidon SR hydrophobic polymer matrix were presented. It was shown that dry and wet granulation could improve the processing properties of mixtures for preparing tablets and provide the required amben release kinetics.

The need to screen the kinetic characteristics of pharmaceuticals in early development stages is justified. The advantages and limitations of cassette dosing in pharmacokinetic investigations are discussed. The dose and the presence or absence of pharmaceutical interactions are shown to be the critical factors affecting the reliability of pharmacokinetic parameters assessed by the cassette method. The hypothesis that toxicokinetic cassette screening of compounds capable of interacting is appropriate for describing the slow elimination phase was verified by comparing lewisite excretion parameters after injection into laboratory animals of lewisite and a mustard-gas—lewisite mixture.

Recent progress on studies of labdane diterpenoids is compiled. Seventy seven biologically active labdane diterpenes isolated from various higher plants, mosses, liverworts, algae, etc. are reported. The absolute configurations of compounds 1 – 77 were established using extensive spectroscopic techniques. The wide range of biological activities possessed by these diterpenoids suggests that thorough evaluation of some structure-activity relationships is overdue. In this review, data on the natural sources, isolation, structure and biological activities of labdane diterpenoids isolated from various plants are summarized.