Pharmaceutical Chemistry Journal (v.45, #7)

Trecrezan as an activator of aminoacyl-tRNA synthase mRNA by M. M. Rasulov; M. K. Nurbekov; S. N. Bobkova; O. A. Belikova; M. G. Voronkov (381-384).
In vitro experiments performed on rabbits showed that tris-2-(hydroxyethyl)ammonium orthocresoxyacetate (trecrezan) increases the cytokine activity of total tryptophanyl mRNA synthase (TRSase) via stimulation of the synthesis of a specific mRNA synthase (TRSase). This explains the mechanisms of the hypolipidemic, immunomodulatory, and adaptogenic actions of trecrezan.
Keywords: trecrezan; mRNA synthase expression; adaptogenic effect

The actions of melatonin on the activity of the glutathione antioxidant system and various NADPH-generating enzymes in rats with type 2 diabetes mellitus were studied. The development of this pathology was found to be accompanied by increases in the activities of glutathione reductase (E.C., glutathione peroxidase (E.C., and NADP-isocitrate dehydrogenase (NADP-IDH, E.C., along with decreases in the activity of glucose-6-phosphate dehydrogenase (G6PDH, E.C. in both the liver and serum as compared with animals without pathology. In addition, there was a decrease in the level of reduced glutathione. Administration of melatonin induced changes in the study parameters towards control values. This effect appeared to be linked to decreases in the loading on the glutathione antioxidant system due to the antioxidant properties of this hormone, which are associated with the features of its chemical structure which allow it to interact efficiently with free radicals to form metabolites with little or no toxicity.
Keywords: Melatonin; type 2 diabetes mellitus in rats; glutathione antioxidant system

Published data on the chemical and biological properties of α-, γ-, and δ-carbolines are reviewed.
Keywords: Pyridoindoles (carbolines); chemical and biological properties of carbolines; pK a values of carbolines

Synthesis of 2-(4-substituted phenyl)-3-[4-substituted piperazino(piperidino)]propan-1-ol dihydrochlorides and their effects on adenosine deaminase activity by A. U. Isakhanyan; G. A. Gevorgyan; O. A. Papoyan; S. S. Mardanyan; I. G. Vermishyan; S. G. Sharoyan; G. A. Panosyan (401-405).
Aminomethylation of 4-substituted acetophenones yielded a series of β-amino-4-substituted propiophenones. Reduction of these with lithium alumohydride in dry ether produced 1-(4-substituted phenyl)-3-[4-substituted piperazino(piperidino)]propan-1-ols, which were then converted to the corresponding dihydrochlorides. The abilities of these compounds to inhibit adenosine deaminase, a key enzyme in purine metabolism in living organisms, were studied. Some of the compounds had quite marked inhibitory effects on the enzyme. The abilities of the compounds synthesized here to inhibit adenosine deaminase were found to depend on their structure. It is of note that virtually all the compounds inhibited the high molecular weight form of the enzyme to a significantly lesser extent than the low molecular weight form.
Keywords: Aminomethylation; β-aminoketones; aminopropanols; adenosine deaminase; inhibition

Recurrent model of acute toxicity in homologous series of organic compounds by V. Yu. Grigor’ev; O. A. Raevskii (406-411).
A simple recurrent equation is proposed as a model describing acute toxicity in homologous series of organic compounds in relation to various biological objects. The recurrent model of toxicity provided better extrapolation than linear and parabolic models. Plotting of The coefficients of recurrent equations plotted on planes defined by these coefficients for types of chemical compounds allowed the nonspecific or specific nature of toxicity in homologous series to be identified. Similar visualization in relation to different types of biological objects allowed toxicological relatedness to be identified on the basis of the distances between them. These results may provide grounds for creating computer programs predicting the acute toxicities of new chemical compounds on the basis of QSAR approaches.
Keywords: Toxicity; recurrent model; homologous series

Gas chromatography–mass spectrometric methods were used to study the component composition of volatile substances and fatty acids in a CO2 extract and the essential oil of the Siberian fir. The essential oil contained 19 identified terpenes, dominated by bornyl acetate, camphene, and carene-3-∆. Seven fatty acids and the triterpene alcohol dihydroabietol were identified in the non-volatile fraction of the CO2 extract.
Keywords: Siberian fir; essential oil; chemical component composition

Essential biopharmaceutical properties of drugs at the gastrointestinal absorption stage (Review) by I. E. Shokhin; Yu. I. Kulinich; G. V. Ramenskaya; V. G. Kukes (415-418).
The essential biopharmaceutical properties affecting the ability of drugs to reach the systemic circulation are discussed. Properties such as biopharmaceutical solubility and intestinal permeability are described, along with methods of assessing them and interactions between drug transport and absorption across GIT membranes and levels of metabolism. The main biopharmaceutical classification systems for drugs are presented and their use in regulatory practice is discussed.
Keywords: Solubility; absorption; permeability; metabolism; biopharmarceutical classification system (BCS); biopharmaceutical drug disposition classification system (BDDCS) based on solubility and metabolism; biowaiver

An improved synthesis of N-(3-phenylbicyclo[2.2.1]-yl)-N-ethylamine hydrochloride (Fencamfamine) by I. A. Novakov; B. S. Orlinson; R. V. Brunilin; M. B. Navrotskii; A. S. Eremiichuk; S. A. Dumler; E. A. Gordeeva (419-422).
We describe here a new and efficient method for synthesis of N-(3-phenyl[2.2.1]bicyclohept-2-yl)-N-ethylamine hydrochloride (Fencamfamine), based on the reduction of trans-5-nitro-6-phenylbicyclo[2.2.1]hept-2-ene with Raney alloy mixed with aqueous NaOH and tetrahydrofuran followed by N-alkylation of the resulting product with 95% ethanol in the presence of skeletal nickel.
Keywords: N-(3-phenyl[2.2.1]bicyclohept-2-yl)-N-ethylamine hydrochloride; Fencamfamine

Techniques for the preparation and analysis of a liposomal formulation of lisomustine by K. V. Kostin; E. V. Ignat’eva; E. V. Tazina; V. M. Pechennikov; N. A. Oborotova (423-426).
The optimal composition and production technique were identified for preparation of liposomal formulations of lisomustine. The stability of this formulation was increased by lyophilization of the liposomal dispersion using a cryoprotector, i.e., 10% sucrose solution. The lisomustine content in lysosomes was assayed by spectrophotometry at a wavelength of 230 nm. Uptake of lisomustine into freshly prepared liposomes amounted to 61.2 ± 0.4% and particle size was 170 ± 20 nm.
Keywords: Liposomes; lisomustine; lyophilization; gel filtration; spectrophotometry

A series of bioactive 3H,7H,8H,11H-9-[(5″-(6′-methyl-2-oxo-2H-[1]-4′-benzopyranoxy)-2″,4″-dihydro-[1″,2″,4″]-triazol-3″-one)methyl]-3,8,11-trioxo-dipyrano[2,3-f;2,3-c]quinoline (4) and 3H,7H,8H,11H-9-[(2′-(3″-phenyl-thiazolidin-4″-one)-phenoxymethyl]-3,8,11-trioxo-dipyrano[2,3-f;2,3-c]quinoline (7) analogs of 3H,7H,8H,11H-9-bromomethyl-3,8,11-trioxo-dipyrano[2,3-f;2,3-c]quinoline (1) have been synthesized and evaluated for their antibacterial activity against Gram-positive bacteria (S. aureus) and Gram-negative bacteria (S. typhi and E. coli). Pyranoquinolines with triazole and thiazolidine moieties exhibited promising antibacterial activity. The structures of all synthesised compounds were confirmed on the basis of analytical and spectral data.
Keywords: 6-Aminocoumarin; bromomethyl-dipyranoquinoline; Schiff’s bases; triazoles; thiazolidine; antimicrobial activity

Synthesis of new 1,2,4-triazoles as anti-inflammatory and anti-nociceptive agents by N. Upmanyu; J. K. Gupta; K. Shah; P. Mishra (433-439).
A series of fifteen new substituted 1,2,4-triazoles (6a – 6o) have been synthesized in order to obtain new agents with potential anti-inflammatory and anti-nociceptive activity. The title compounds were synthesized using 4-methylbenzoic acid as a starting reactant. The synthesized compounds were characterized by spectroscopic methods (IR, 1H NMR, 13 C NMR, FAB+ − MS) and elemental analysis (nitrogen analysis). The title compounds were evaluated for anti-inflammatory activity by the carrageenan induced paw edema method, and some compounds were evaluated for anti-nociceptive activity by the hot plate method and tail immersion method. Compounds N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]-2-piperidin-1-ylacetamide (6f), 2-(4-benzylpiperazin-1-yl)-N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]acetamide (6i) and N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]-2-morpholin-4-ylacetamide (6 k) showed significant anti-inflammatory activity compared to other synthesized compounds, and N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]-2-morpholin-4-ylacetamide (6 k) exhibited superior anti-nociceptive activity.
Keywords: 1,2,4-Triazoles; cyclization; anti-inflammatory activity; anti-nociceptive activity

Assay of ascorbic acid, thiamine, riboflavin, nicotinamide, and pyridoxine in “hexavit” by HPLC by S. Yu. Garmonov; I. A. Salakhov; G. R. Nurislamova; R. N. Ismailova; É. A. Irtuganova; V. F. Sopin (440-443).
A method for the assay of ascorbic acid, thiamine, riboflavin, nicotinamide, and pyridoxine in Hexavit was developed using HPLC. The conditions for chromatographic separation of vitamin mixtures with gradient elution in acidic medium on a reverse phase Discovery RP Amide C16 column were established. This method was verified by analysis of industrial vitamin formulations.
Keywords: HPLC; quality control; water-soluble vitamins

Development of a method for assessing the stability of afobazole by HPLC by L. N. Grushevskaya; N. I. Avdyunina; B. M. Pyatin (444-448).
The aim of the present work was to develop a method for assaying afobazole in substance and medicinal formulations for assessment of the contents of both technical contaminants and likely degradation products. Studies were performed using HPLC on a liquid chromatogram with a spectrophotometric detector in the following conditions: a Phenomenex column (250 × 4.6 mm, sorbent Luna C18(2), 5 μm); mobile phase: acetonitrile, methanol and 0.02 M potassium hydrogen phosphate pH 7.3 solution at a ratio of 100:100:240 (by volume). A method was developed allowing separation of afobazole and its initial and intermediate synthesis products, oxidation products, and other afobazole degradation products produced in acidic and alkaline media and on oxidation and exposure to sunlight. This method yields data on the stability of the substance and medicinal formulations both during preparation and on storage.
Keywords: Afobazole; stability; high-performance liquid chromatography