Pharmaceutical Chemistry Journal (v.44, #3)

Synthesis, antitumor, and anti-monoamine oxidase properties of 2,4,4-trisubstituted triazolobenzo[h]quinazolines by A. I. Markosyan; S. V. Dilanyan; F. G. Arsenyan; R. S. Sukasyan; I. S. Sarkisyan; B. T. Garibdzhanyan (111-114).
The interaction of 1-amino-3-methyl-3-ethyl-3,4-dihydronaphthaline-2-carbonitrile (I) with propanoic acid chloranhyride was used to synthesize the corresponding amidonitrile II, which was then cyclized to form 2,5-diethyl-5-methyl-4-oxo-5,6-dihydrobenzo[h]quinazolin-4(3H)-one (III). Interaction of aminonitrile I with triethylorthoformate and carboxylic acid hydrazides yielded 2-substituted 4-methyl-4-ethyl-4,5-dihydrobenzo[h][1, 2, 4] triazolo[1,5-c]quinazolines (IV-XVIII). The antitumor and anti-monoamine oxidase properties of the compounds obtained were studied.
Keywords: Benzo[h]quinazoline; cyclization; antitumor and anti-monoamine oxidase activity

Synthesis and antitumor properties of amino acids acylated with 2-methyl-3-oxo-1-phenyl-1cyclopentane carboxylic acid by A. O. Martirosyan; S. P. Gasparyan; M. V. Aleksanyan; V. E. Oganesyan; V. V. Martirosyan; A. A. Chachoyan; B. T. Garibdzhanyan (115-116).
Acylation of the silyl esters of amino acids, specifically glycine, f-alanine, sarcosine, glycylglycine, and 6-aminopenicillanic acid, with 1-phenyl-3-oxo-2-methyl-1-cyclopentane carboxylic acid chloride yielded new analogs of the known antitumor antibiotic sarcomycin. The resulting compounds had high levels of antitumor activity.
Keywords: Acylation; amino acid silyl esters; 6-aminopenicillanic acid; 1-phenyl-3-oxo-2-methyl-1-cyclopentane carboxylic acid; dihydrosarcomycin

Synthesis and pharmacological activity of salts of 3-acetyl-2-R-9-dialkylaminoethylimidazo[1,2-a]benzimidazoles by V. A. Anisimova; A. A. Spasov; I. E. Tolpygin; V. A. Kosolapov; A. F. Kucheryavenko; N. A. Gurova; O. Yu. Grechko; N. V. Kirillova; L. V. El’tsova; L. V. Naumenko; V. D. Sysueva (117-122).
New water-soluble 3-acetyl-2-R-9-dialkylaminoethylimidazo[1,2-a]benzimidazoles were synthesized on the basis of previously described structure-effect relationships among imidazobenzimidazole derivatives with high levels of hypotensive activity. All these compounds were studied in vitro in terms of a variety of types of pharmacological activity characteristic for this class of compounds, including antiarrhythmic, antiaggregant, antioxidant, hemorheological, K-opioid agonistic, hypotensive, spasmolytic, and adrenoblocking activities; their effects on cAMP phosphodiesterdase activity and physical exercise tolerance were also studied.
Keywords: Synthesis; imidazo[1,2-a]benzimidazoles; methylketones; antiarrhythmic activity; antiaggregant properties; hemorheological activity; hypotensive action

Synthesis and antioxidant activity of aminomethylated 6-methyluracil derivatives by Yu. N. Chernyshenko; A. G. Mustafin; A. R. Gimadieva; I. B. Abdrakhmanov; A. Ya. Gerchikov; I. V. Safarova (123-125).
The Mannich reactions of 6-methyluracil and 5-nitro-6-methyluracil with piperidine, morpholine, and triazole were studied. The antioxidant activities of the Mannich bases were comparable to that of the known antioxidant ionol.
Keywords: 6-Methyluracil derivatives; synthesis; antioxidant activity

Synthesis and antifungal activity of sulfides, sulfoxides, and sulfones based on (1S)-(-)-β-pinene by V. V. Gavrilov; V. A. Startseva; L. E. Nikitina; O. A. Lodochnikova; O. I. Gnezdilov; S. A. Lisovskaya; N. I. Glushko; E. N. Klimovitskii (126-129).
Attachment of 2-mercaptoethanol and thioglycolic acid methyl ester to the double bond of (1S)-(-)-β-pinene yielded pinane sulfides with the cis configuration. Oxidation of sulfides with m-chloroperbenzoic acid yielded the corresponding sulfoxides and sulfones. The resulting compounds were screened for antimycotic activity and the dynamics of changes in antifungal properties in sulfides-sulfoxide-sulfone series were studied.
Keywords: Pinane sulfides; sulfoxides; and sulfones; antifungal activity

Synthesis and antimicrobial activity of pyrimidinophanes containing a uracil moiety and a bridging sulfur atom by A. E. Nikolaev; V. É. Semenov; A. D. Voloshina; N. V. Kulik; V. S. Reznik (130-133).
Pyrimidinophanes containing one 5(6)-alkylsubstituted uracil moiety and a 10-or 12-methylene bridge including a sulfur atom were synthesized. The bridging S atoms of the macrocycles were converted to sulfonium groups by interaction with para-toluenesulfonate methyl or nonyl esters. The resulting amphiphilic pyrimidinophanes were tested for bacteriostatic and fungistatic activity against Gram-positive and Gram-negative bacteria and fungi. Amphiphilic pyrimidinophanes with 5-decyl-6-methyluracil moieties had high levels of bacteriostatic activity against Gram-positive bacteria. The minimum inhibitory concentration of the macrocycle containing a methyl group in the sulfonium grouping against Staphylococcus aureus was 0.75 !g/ml. These data are of value in seeking new highly effective antimicrobial agents.
Keywords: Pyrimidinophanes; uracils; sulfonium group; antibacterial activity

The reactions of 6-acyl-7-aryl-4,7-dihydrotetrazolo [1,5-a]pyrimidin-5-carboxylates with hydrazine hydrate were used to synthesize 8-methyl-9-aryl-and 8,9-diaryl-4,9-dihydrotetrazolo [1',5':1,2]pyrimidino[4,5-d]pyrazin-5-ones (I – XXX). Compounds I – XXX were found to have moderate antimicrobial activity.
Keywords: Synthesis; tetrazole derivatives; antimicrobial activity

The effects of polyphenol-containing hepatoprotectors of plant origin, i.e., an extract of the Russian thistle and silymarin, on liver metabolism after paracetamol-induced damage were studied in rats. Both hepatoprotectors decreased the signs of paracetamol hepatotoxicity and promoted recovery of the major functions of the liver. Russian thistle extract and to a lesser extent silymarin prevented the formation of lipid peroxidation products, i.e., diene conjugates, Schiff bases, and malondialdehyde, in the liver, produced reductions in blood aminotransferases, y-glutamyltranspeptidase, acid and alkaline phosphatases, and phospholipase A levels, decreased the total bilirubin concentration, and activated the detoxification of bilirubin, phenols, and ammonia.
Keywords: Russian thistle extract; silymarin; hepatoprotectors

Antihypoxic and hemostimulating actions of a nettle extract prepared by a nanotechnological approach by V. N. Burkova; S. G. Boev; A. I. Vengerovskii; N. V. Yudina; A. G. Arbuzov (141-143).
Studies using models of hypobaric and hemic hypoxia in mice and circulatory impairment induced by lead acetate showed that a nettle leaf extract dispersed into nanoparticles increased the survival rate, prolonged the time to death, prevented gastric ulceration, increased blood erythrocyte and leukocyte counts and hemoglobin levels, and decreased prothrombin time, the effects being greater than those obtained with a nettle leaf extract prepared by grinding to a particle size of 1 mm. The antihypoxic action of the nettle leaf extract prepared by nanotechnological methods was as great as the effect of a Rhodiola extract, while the hemostimulatory action was no less than that of ferrous sulfate.
Keywords: Nettle extract; antihypoxic and hemostimulatory effects

Standardization of chaga tincture and befungin by E. N. Zhukovich; M. Yu. Semenova; L. A. Sharikova; T. F. Pribytkova (144-146).
Methods for standardizing the formulations Chaga Tincture and Befungin were developed, consisting of extraction of the non-phenol fraction predominantly containing tetracyclic triterpenes, including lanosterol and ergosterol, followed by spectrophotometry of colored complexes with vanillin in acidic conditions. The contents of tetracyclic triterpenes expressed as lanosterol ranged from 0.01% to 0.035% in Chaga Tincture and from 0.01% to 0.02% in Befungin.
Keywords: Chaga; standardization; colored complex; spectrophotometry; non-phenol fraction; tetracyclic triterpenes; lanosterol

Diffusion-transport properties of a polycomplex matrix system based on eudragit® EPO and Carbomer 940 by R. I. Mustafin; T. V. Kabanova; E. R. Zhdanova; A. V. Bukhovets; V. R. Garipova; Sh. F. Nasibullin; V. A. Kemenova (147-150).
New interpolyelectrolyte complexes (IPEC) between Eudragit® EPO (EPO) and Carbomer 940 (C940) were synthesized for assessment as controlled-release delivery carriers for oral systems. Depending on the structural properties, the resulting IPEC were distinct from the individual (co)polymers and their physical mixtures in terms of their swelling profiles in media simulating the gastrointestinal tract. Changes in structure and composition occurring within the polycomplex matrix on swelling were studied by IR spectroscopy, MT-DSC (modulated temperature differential scanning calorimetry), and elemental analysis. The mechanism underlying the transport of the model drug ibuprofen from the polycomplex matrix was identified.
Keywords: Polycomplex; controlled release; ibuprofen; Eudragit® ; Carbomer 940

Effects of technical parameters on the physicochemical properties of rifampicin-containing polylactide nanoparticles by O. O. Maksimenko; L. V. Vanchugova; E. V. Shipulo; G. A. Shandryuk; G. N. Bondarenko; S. É. Gel’perina; V. I. Shvets (151-156).
The aim of the present work was to assess the influences of the parameters of the process of preparing polylactide-based nanosomal medicinal formulations of rifampicin (Rif) on nanoparticle size, the level of Rif sorption, and the kinetics of Rif release in vitro. The most effective Rif sorption in nanoparticles (up to 90%) was obtained using polylactides with additional terminal carboxyl groups. An increase in the initial Rif concentration in the organic phase from 1 to 5 mg/ml led to some decrease in the extent of sorption (from 89% to 76%) though it had no significant effect on the sizes of the resulting nanoparticles (190 – 260 nm). The rate of Rif release could be controlled by altering the composition of the polymer matrix of the nanoparticles; the presence of additional terminal carboxyl groups in polylactides gave slower antibiotic release, resulting from tighter interaction with the polymer matrix.
Keywords: Nanoparticles; polylactides; rifampicin

Determination of some surface-active characteristics of solutions of triterpene saponin derivatives of oleanolic acid by N. V. Mironenko; T. A. Brezhneva; T. N. Poyarkova; V. F. Selemenev (157-160).
The surface-active characteristics of triterpene saponin derivatives of oleanolic acid were determined: the critical micelle concentration, the surface activity, the absorption layer thickness, the area per molecule, etc. These results will be of value in predicting, executing, and intensifying various processes involving these substances.
Keywords: Triterpene saponins; surface-active characteristics; assessment; micelle formation

Spectrophotometric assay of ethamsylate using a tetrazolium salt by O. A. Tarkhanova; S. A. Vasyuk (161-165).
A spectrophotometric assay method for ethamsylate in prepared medicinal formulations and biological fluids was developed. The method is based on the reduction of p-nitrotetrazolium chloride by ethamsylate in n-propanol in the presence of sodium hydroxide followed by measurement of the optical density of the resulting colored solution at λmax = 490 nm. The detection limit was 0.32 μg/100 ml. The plot was linear over the range 0.48 – 1.12 mg/ml with a correlation coefficient of 0.9998. As compared with other techniques, this method is simple to perform, accurate, reproducible, and sensitive. The results are consistent with results obtained by methods in Analytical Normative Documents (AND), supporting the suitability of the present method.
Keywords: Ethamsylate; p-nitrotetrazolium chloride; spectrophotometric assay; medicinal formulations; serum