Pharmaceutical Chemistry Journal (v.42, #3)

Complex approach to investigation of the mechanisms of action of antimicrobial and antiviral drugs by V. A. Bykov; V. A. Dubinskaya; L. B. Rebrov; M. F. Mineeva; S. G. Skuridin; Yu. M. Evdokimov (105-110).
Enzyme and biosensor test systems have been used in vitro to study the possible mechanisms of action of antimicrobial and antiviral drugs. It is established that compounds belonging to these groups of drugs may cause various modes of damage in the DNA secondary structure, possess complex-forming properties, inhibit enzymes of the antioxidant protection system of the oganism, induce energy deficiency, and lead to the storage of toxic metabolites (aldehydes).

Antitumor steroids. 3. Synthesis and biological activity of 11β-hydroxyestra-1,3,5(10)-triene derivatives with bis-(2-chloroethyl)amino-containing substituents in the 3-position by V. M. Rzheznikov; L. E. Golubovskaya; E. E. Mayatskaya; B. I. Keda; L. P. Sushinina; T. A. Titova; V. N. Tolkachev; I. P. Osetrova; Z. S. Smirnova (111-114).
A series of antitumor compounds combining cytotoxic and estrogen action have been synthesized on the basis of 11β-acyloxyestra-1,3,5(10)-trienes. The corresponding synthons, 11β-hydroxy derivatives of estrone, estradiol, and ethynylestradiol, were obtained by oxidative nitration of 3-mono-and 3,17-diesters of these estrogens with ceric ammonium nitrate into the corresponding 9α-hydroxy-and 11β-nitroxy analogs with subsequent hydrogenolysis of the 9-hydroxy groups and removal of the nitrate protecting groups.

Synthesis and antitumor activity of new 5-(4-alkoxybenzyl)pyrimidines by L. A. Grigoryan; M. A. Kaldrikyan; R. G. Melik-Ogandzhanyan; F. G. Arsenyan (115-117).
Reactions of 2-methylthio-4,6-dichloro-5-(4-alkoxybenzyl)pyrimidines with aliphatic and aromatic primary and secondary amines and sodium methoxide were used to synthesize the corresponding 4-amino-and 4-methoxy-6-chloropyrimidines. The antitumor properties of the synthesized compounds have been studied.

Antimonoamineoxidase and antitumor activity of 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines by A. I. Markosyan; S. V. Dilanyan; R. S. Sukasyan; F. G. Arsenyan; B. T. Garibdzhanyan (118-121).
Reactions of 3-methyl-3-ethyl-1-amino-2-cyano-3,4-dihydronaphthalene (I) with carboxylic acid chlorides lead to the formation of either monoacylated (II–VII) or diacylated (VIII–X) products depending on the amount of reactants. When dry hydrogen chloride is bubbled through alcohol solutions of the amides (II–VII), these compounds cyclize to 2-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (XI–XVI). Alkylation of benzo[h]quinazolines XI and XII yielded 3-substituted benzo[h]quinazolines (XVII–XIX). Antitumor and antimonoamineoxidase properties of the synthesized compounds have been studied. Experiments in vitro have shown that some of these compounds exhibit antimonoamineoxidase activity. Compounds II and IV showed weak inhibition of Ehrlich’s ascites carcinoma (by 30 and 47%, respectively) at doses of 100–250 mg/kg in chemotherapeutic experiments.

Liquid extraction of ginseng and bilberry leaves by D. V. Demchenko; Yu. D. Papok; A. B. Legosteva (122-126).
The number of diabetes patients continuously increases. Combined application of synthetic drugs and phytopreparations can decrease the negative side effects of drugs. The aim of this study was to create a new antidiabetic drug in the form of a liquid extract based on dry bilberry (Vaccinium myrtillus L.) and ginseng leaves. Quantification of flavonoids in bilberry leaves was carried out using a spectrophotometric method (425 nm); of tannins, by titration. Extraction performed with 50% aqueous ethanol isolated the maximum amount of principal active substances (polyphenols, ginsenosides). The optimum extraction conditions were determined as 4.5 h (time of infusion) and 5 h (time of displacement). Characteristics of the liquid extract are a brown fluid with distinctive odor, bittersweet, ethanol content 46.70 ± 0.31%, and solid residue content 35.23 ± 0.27%. The tannin content that was determined qualitatively using the reaction with FeNH4(SO4)2 · 12H2O (development of a dark-green color) and with 1% gelatin solution (formation of impurities) was 13.97 ± 0.22%. The flavonoid content that was determined by TLC (silica gel; butanol: acetic acid:water, 60:20:20; 3 spots of flavonoids) was 0.79 ± 0.03%. The panaxozide content that was determined by TLC (silica gel; butanol:ethanol:NH4OH (25%), 9:2:5; 8 spots of panaxozides) was 0.29 ± 0.02%.

Electric-field-assisted extraction of antioxidants from bearberry leaves by N. Yu. Gribova; N. I. Belaya; T. A. Filippenko; A. N. Nikolaevskii; A. V. Belyi; V. A. Zaets (127-129).
Conditions for improving the extraction of substances with antioxidant properties from bearberry (Arctostaphylos Adams) leaves have been studied. It is established that the natural antioxidants are most completely extracted by maceration in a constant electric field (U = 35 V, I = 250 mA) for 2 h at 303 K with stirring. The optimum extractant is 1% aqueous acetic acid with added surfactant (Tween-80, 8.8 × 10− 4 M). This extract increases the stability (storage time) of sunflower oil more than four times. The proposed method of electroextraction increases the yield of extracted substances with antioxidant properties and decreases the yield of ballast substances without complicating the procedure and increasing the consumption of materials.

Investigation of the oil extract of Schizandra seeds by E. N. Zhukovich; M. Yu. Semenova; L. A. Sharikova; T. F. Pribytkova; S. Yu. Bokareva; L. M. Korovina (130-133).
A method for production and standardization of the oil extract of Schisandra chinensis seed has been developed based on isolation of the lignan fraction (with the major constituent schizandrol A) by aqueous ethanol (20%) and spectrophotometric assay. Solutions used for the quantitative assay are concentrated and then used for TLC (qualitative analysis). HPLC data showed that the concentration of the lignan fraction (schizandrol A) amounts to 0.08–0.11%, which is close to that in commercial tincture (about 0.09%) and that the proposed oil extract can be used as a neurotonic stimulant in the same doses as the tincture.

Features of hydrocortisone C6-alkylation by V. A. Andryushina; T. S. Stytsenko; T. S. Savinova; K. G. Skryabin; G. S. Grinenko (134-141).
Two methods of C6-alkylation of hydrocortisone, C6-formylation and direct methylenation, have been studied. It is shown that both methods are effective and can be of practical interest because they can produce 6α-methylhydrocortisone from hydrocortisone with an overall yield of 50–55%. A short and convenient pathway has been found for producing Δ9(11)-6α-methylcorticosteroids used as intermediates in the synthesis of highly active 6α-methyl-9α-halo-substituted hydrocortisone derivatives.

Synthesis of taurine by O. M. Bondareva; D. V. Lopatik; Z. I. Kuvaeva; L. G. Vinokurova; M. M. Markovich; I. P. Prokopovich (142-144).
Taurine (2-aminoethanesulfonic acid) has been synthesized via reaction of 2-aminoethylsulfuric acid (prepared from monoethanolamine and sulfuric acid) with sodium sulfite. The target compound was separated from the excess of sodium sulfite by extraction with conc. aqueous ammonia (25%).

Development of a nanosomal formulation of moxifloxacin based on poly(butyl-2-cyanoacrylate) by E. V. Shipulo; I. I. Lyubimov; O. O. Maksimenko; L. V. Vanchugova; E. A. Oganesyan; P. G. Sveshnikov; S. F. Biketov; E. S. Severin; L. B. Heifets; S. E. Gel’perina (145-149).
A nanosomal formulation of moxifloxacin has been prepared by anionic polymerization of poly(butyl-2-cyanoacrylate) in the presence of the drug. The poly(butyl-2-cyanoacrylate) nanoparticles absorb effectively moxifloxacin with a high total content and have a considerable capacity (> 45%). The influence of reaction parameters such as pH and drug-to-polymer ratio on the nanoparticle characteristics has been studied. The efficacy of the novel formulation has been evaluated in mice infected with M. tuberculosis. It is shown that the efficacy of the proposed nanosomal formulation for i.v. administration evaluated by a decrease in the lung mycobacteria count is more than twice that of a reference preparation.

Ionometric determination of cefotaxime in biological media by O. I. Kulapina; V. V. Baraguzina; N. V. Skoblikova (150-152).
Ion-selective electrodes based on ion exchangers of tetradecylammonium (TDA) with cefotaxime (claforan) anions have been developed. The proposed electrodes are sensitive to cephalosporins in the concentration range from 1 × 10− 5 to 1 × 10− 1 M. The time for establishing a steady-state potential is 1–2 min. The potential drift does not exceed 2 mV/d. The detection threshold for cefotaxime is 3.6 × 10− 5 M in the optimum pH range of 4.3–6.5. Comparison of the main electrochemical characteristics of the ion-selective electrodes based on TDA associates with cephalosporins showed that the best parameters are found in electrodes with membranes containing claforan.

Quantitative HPLC determination of phenolic compounds in yarrow by R. Benetis; J. Radusiene; V. Jakstas; V. Janulis; G. Puodziuniene; A. Milasius (153-156).
The qualitative and quantitative compositions of flavonoids (vicenin-2, luteolin-3′-di-O-glycoside, luteolin-7-O-glycoside, rutin, apigenin-7-O-glycoside, luteolin, apigenin) and chlorogenic acid in herb, leaves, and stems of yarrow (Achillea millefolium) samples collected in the Kaunas region of Lithuania have been studied by means of high-performance liquid chromatography (HPLC). It is established that these substances exhibit a characteristic distribution with predominant formation of apigenin-7-O-glycoside and luteolin-7-O-glycoside among the identified flavonoids in the herb of yarrow whereas the leaves contain predominantly chlorogenic acid, rutin, and apigenin-7-O-glycoside; the stems, predominantly chlorogenic acid, rutin, apigenin-7-O-glycoside, and luteolin-7-O-glycoside. The results can be used to choose selection donors of this medicinal plant material.