Pharmaceutical Chemistry Journal (v.47, #2)

Structural effects induced by gold nanoparticles in particles of cholesteric liquid-crystalline dispersion of double-stranded nucleic acids by S. G. Skuridin; V. I. Salyanov; V. I. Popenko; E. V. Shtykova; E. S. Lisitsyna; V. A. Dubinskaya; V. A. Bykov; Yu. M. Evdokimov (71-79).
Gold (Au) nanoparticles of diameter ~2 nm (but not 5 or 15 nm) were capable of incorporating effectively into quasi-nematic layers of particles of cholesteric liquid-crystalline dispersions (CLCD) formed by double-stranded nucleic acids of various families [B-form DNA, A-form poly(I) × poly(C)]. A study of the properties of CLCD particles treated with Au nanoparticles by various physicochemical methods demonstrated that incorporation of Au nanoparticles into quasi-nematic layers of these particles resulted in two effects. First, it caused rearrangement of the spatial cholesteric structure of LC dispersion particles that was accompanied by a decrease in the amplitude of the anomalous band in the circular dichroism spectrum of the corresponding initial CLCD. Second, it induced Au cluster formation within the LC particles that was accompanied by the appearance of a surface plasmon resonance band in the visible spectral region. It was possible that these structural effects were responsible for the genotoxicity of the Au nanoparticles.
Keywords: DNA; liquid-crystalline dispersions of DNA; gold nanoparticles; circular dichroism; absorption spectroscopy; small-angle scattering; surface plasmon resonance; structure of lyotrophic liquid crystals; toxicity of nanoparticles

11β-Hydroxysteroid dehydrogenase (11β-HSD1) is an enzyme that catalyses the transformation of the inactive glucocorticoid cortisone into active cortisol. A chronically elevated level of cortisol as a result of 11β-HSD1 hyperexpression in the liver and fatty tissue leads to the development of metabolic syndrome, obesity, insulin-resistance, type 2 diabetes mellitus (DM2), and cardiovascular complications. Inhibition of 11β-HSD1 is recognized as a promising strategy for reducing the activity of glucocorticoids on a tissue-specific level. Herein inhibitors of 11β-HSD1, representatives of several types of N-containing heterocycles at various research stages, are reviewed as potential drugs influencing metabolic syndrome, DM2, and obesity.
Keywords: 11β-hydroxysteroid dehydrogenase; cortisol; metabolic syndrome; obesity; drug discovery

Synthesis and Biological Activity of Fullerenols with Various Contents of Hydroxyl Groups by M. Yu. Eropkin; E. Yu. Melenevskaya; K. V. Nasonova; T. S. Bryazzhikova; E. M. Eropkina; D. M. Danilenko; O. I. Kiselev (87-91).
Polyhydroxyfullerenes, fullerenols with various contents of hydroxy groups, C60(OH)12 – 14, C60(OH)18 – 24, and C60(OH)30 – 38, were synthesized. The first group was insoluble in water and exhibited no biological activity when introduced into cell cultures as suspensions. The other two versions of fullerenols possessed a broad spectrum of antiviral activity in vitro against actual strains of human influenza virus A(H1N1) and A(H3N2), avian influenza A(H5N1), human herpes simplex virus, adenovirus, and respiratory-syncytial virus. The water-soluble versions of fullerenol were non-toxic in vitro toward human and animal cells of various tissue origins. Besides the antiviral activity, the fullerenols demonstrated a protective effect against UVA-induced phototoxicity. The fullerenol version C60(OH)18 – 24 had the maximum biological activity for all studied parameters. The soluble biologically active versions of fullerenol could find application in pharmacology because they could serve as a basis for new effective and non-toxic antiviral and cytoprotective drugs.
Keywords: fullerenols; antiviral activity; UVA-protective effect; cell cultures

Synthesis and anticonvulsant activity of condensed thieno[2,3-e]pyrrolo[1,2-a]pyrimidin-8,12-diones by E. G. Paronikyan; Sh. F. Akopyan; A. S. Noravyan; S. S. Mamyan; R. G. Paronikyan; I. A. Dzhagatspanyan (92-95).
New condensed thieno[2,3-e]pyrrolo[1,2-a]pyrimidin-8,12-ones were synthesized from 2-thioxo-1,2-dihydropyridine-3-carbonitriles. The synthesized compounds were shown to exhibit pronounced anticonvulsant activity for corazole convulsions.
Keywords: synthesis; condensed pyrrolo[1,2-a]pyrimidines; corazole; anticonvulsant activity

Synthesis and antioxidant activity of [(1-aryl-5-formylimidazol-4-yl)thio]acetic acids by V. A. Chornous; A. A. Palamar; I. N. Yaremii; M. V. Vovk (96-98).
A series of [(1-aryl-5-formylimidazol-4-yl)thio]acetic acids were synthesized by condensation of 1-aryl-4-chloroimidazol-5-carbaldehydes with thioglycolic acid. The obtained compounds exhibited pronounced antioxidant activity in the concentration range 10 –1 – 10–3 M.
Keywords: 1-aryl-4-chloroimidazol-5-carbaldehydes; [(1-aryl-5-formylimidazol-4-yl)thio]acetic acids; thiotriazoline; antioxidant activity

Rheological properties of an original pharmaceutical composition of a nanostructured silver system stabilized by arabinogalactan by T. V. Romanko; Ya. A. Kostyro; E. N. Gumennikova; K. V. Alekseev; V. G. Romanko; L. A. Grishchenko; L. A. Yes’kova; L. A. Ostroukhova; V. A. Babkin; B. A. Trofimov (99-102).
Rheological properties of an original pharmaceutical composition of a nanostructured (ultradisperse) silver system stabilized by arabinogalactan were studied by dynamic rheology and compared with the official silver- containing preparation dermazin. Significant differences were observed in the rheological characteristics of the soft dosage forms that affected their adherence to skin, the bioavailability of the active ingredients, and the production technology. It was established that the original pharmaceutical composition of the ultradisperse silver system stabilized by arabinogalactan was a structured liquid with clearly pronounced non-Newtonian flow characteristics that exhibited viscoplastic and thixotropic properties. Its rheological parameters corresponded well to requirements for the technical rheological optimum for extrusion of hydrophilic gels.
Keywords: silver–arabinogalactan nanocomposite; rheological properties; rheological optimum for extrusion of hydrophilic gels

14α-Hydroxylation of steroids by mycelium of the mold fungus Curvularia lunata (VKPM F-981) to produce precursors for synthesizing new steroidal drugs by V. A. Andryushina; N. E. Voishvillo; A. V. Druzhinina; T. S. Stytsenko; V. V. Yaderets; M. A. Petrosyan; O. A. Zeinalov (103-108).
Five 14α-hydroxylated derivatives of androstane and pregnane steroids were obtained using mycelium of the mold fungus Curvularia lunata (VKPM F-981). The conditions for microbiological transformation of androst-4-en-3,17-dione that enabled its 14α-hydroxy analog to be obtained in yields up to 60% with substrate loading 6 g/L were determined. The 21-acetoxy analog of proligestone was synthesized from 14α-hydroxycortexolone that was formed simultaneously with hydrocortisone during hydroxylation of cortexolone by C. lunata. The resulting 14α- and 14α,21-hydroxysteroids could be used as precursors for the synthesis of new drugs.
Keywords: 14α-hydroxysteroid derivatives; Curvularia lunata ; hydroxylation

Pecularities of determining the content of 3-substituted 4-hydroxycoumarins in disinfectants and drugs by A. N. Kochetov; K. A. Shestakov; G. M. Shpilevskii; L. G. Kuz’mina (109-117).
Aspects of the analytical determination of pharmacologically active 4-hydroxycoumarin derivatives that are used for therapeutic purposes and in medical disinfection practice were reviewed. The possibility of determining jointly six derivatives of this series in various objects using reversed-phase HPLC with UV detection was shown.
Keywords: 4-hydroxycoumarins; RP HPLC; rodenticides

The possibility of using caproic and cyclohexanecarboxylic acids for determining sorbic and benzoic acids, respectively, was studied. The presence of double bonds in sorbic and benzoic acids decreased significantly their retention times compared with those of their saturated analogs (caproic and cyclohexanecarboxylic acids) on chromatography columns with alkyl substituents. The presence of double bonds had a smaller effect on the retention of the compounds on columns with phenyl and nitrile substituents. Sorbic and benzoic acids could not be separated on chromatographic columns with alkyl substituents if the studied mobile phases [MeOH, 20 mMKH2PO (pH 3.0) or MeCN, 20 mMKH2PO4 (pH 3.0)] were used. However these acids were separated on columns with nitrile and phenyl sorbents. The best separation of the acids was achieved on a Diasphere C10CN column.
Keywords: HPLC; sorbic acid; benzoic acid

Optimum parameters for ergocalciferol determination by thin-layer chromatography by O. V. Trineeva; E. F. Safonova; A. I. Slivkin; E. V. Borodina (121-123).
Optimum conditions for vitamin D2 determination by thin-layer chromatography (TLC) were established. It was shown that a theoretical approach to selecting the parameters of ergocalciferol determination was possible.
Keywords: vitamin D2 ; thin-layer chromatography