Pharmaceutical Chemistry Journal (v.44, #6)

The hypolipidemic action of trecrezan and its possible molecular mechanisms by M. M. Rasulov; M. K. Nurbekov; S. N. Bobkova; V. V. Bulanova; E. S. Antonova; M. I. Susova; M. G. Voronkov (287-290).
The experiments reported here demonstrated that prophylactic use of trecrezan delayed the development of atherosclerosis in rabbits, with decreases in aortic atherosclerotic plaques and reductions in cholesterol, triacylglycerols, and β-lipoprotein levels in serum, liver, and aortic tissue. Trecrezan accelerated the synthesis of tryptophanyl tRNA synthetase, which is the key component in the complex mechanism of action of this agent.
Keywords: Tryptophanyl tRNA synthetase; hypolipidemia; trecrezan; atherosclerosis

Antitumor effects of the combination of magnetohydrodynamic thermochemotherapy and magnetic resonance tomography by N. A. Brusentsov; V. A. Polyanskii; Yu. A. Pirogov; A. I. Dubina; A. A. Uchevatkin; D. A. Kupriyanov; D. A. Tishchenko; P. I. Nikitin; T. N. Brusentsova; T. I. Ksenevich; M. P. Nikitin; E. R. Vol’ter; A. V. Ivanov (291-295).
Fe3O4 nanoparticles were coated with a layer of citric acid, forming coordination bonds between citrate ions and iron ions. The resulting aqueous citrate ferrite colloid was used as a T2-weighted MRI negative contrasting agent. Sequential i.v. doses of citrate ferrite and Magnevist led to increases in MRI image contrast for 40 h and brightness for 30 min; scanning using a Bruker Biospec BC 70/30 USR biospectrotomograph yielded enhanced MRI images. This enhancement of MRI images was used to monitor oncogenesis during magnetohydrodynamic thermochemotherapy (MT) of mammary adenocarcinoma Ca 755 in female C57Bl/6j mice. Dextran ferrite colloid containing cyclophosphamide was tested as a magnetically directed antitumor agent using MT. Treatment of non-infiltrating tumors of volume ≈ 30 mm3 with six sessions of MT each lasting 30 min at 46°C led to 40% tumor regression and 300% increases in survival time. Treatment of infiltrating tumors of volume ≈ 300 mm3 in the same conditions yielded a 200% increase in survival time.
Keywords: Citrate ferrite; negative MRI; Ca 755; dextran ferrite

Synthesis and antifungal activity of 3-hydroxy-7,7-dialkyl-7,8-dihydroindolo[2,1-a]isoquinolinecarboxylic acid amides by O. V. Surikova; A. G. Mikhailovskii; N. N. Pershina; G. A. Aleksandrova; V. V. Semeriko; M. I. Vakhrin (296-298).
Reaction of enaminoamides of the 1,2,3,4-tetrahydroisoquinoline series with p-benzoquinone yielded 3-hydroxy-7,7-dialkyl-7,8-dihydroindolo[2,1-a]-isoquinolinecarboxylic acid amides. Use of benzo[f]isoquinoline as the enamine resulted in synthesis of the relatively unknown benzo[f]indolo[2,1-a]isoquinoline system. The fungicidal activity of the compounds synthesized here was studied and the most active was the hexamethyleneimide, which was active at a concentration of 500 μg/ml.
Keywords: Synthesis; 3-hydroxy-7,7-dialkyl-7,8-dihydroindolo[2,1-a]-isoquinolinecarboxylic acid amides; antifungal activity

Synthesis and antiviral activity of 18α-glycyrrhizic acid and its esters by L. A. Baltina Jr.; O. V. Stolyarova; L. A. Baltina; R. M. Kondratenko; O. A. Plyasunova; A. G. Pokrovskii (299-302).
New esters (sulfate, nicotinates, and 4-methoxycinnamate) of 18α-glycyrrhizic acid (18α-GA) were synthesized; these were D/E-trans-isomers of natural 18β-GA (GA), which is the major triterpene glycoside in the roots of Spanish licorice and Urals licorice (Glycyrrhiza glabra L. and Gl. uralensis Fisher). Changes in the stereochemistry of the GA aglycone led to significant decreases in its anti-HIV-1 activity.
Keywords: 18α-glycyrrhizic acid; esters; anti-HIV activity

The biological activities of 4-(1H-azol-1-ylmethyl)benzoic acid hydrazides were assessed by studying leukocyte responses to these compounds. The study compounds were found to have stimulatory actions on the body’s general resistance mechanisms.
Keywords: 4-(1H-azol-1-ylmethyl)benzoic acid hydrazides; synthesis; rat leukocyte system

Preparation and use of N-acetyl-α-amino acids by Z. I. Kuvaeva; D. V. Lopatik; T. A. Nikolaeva; A. N. Knizhnikova; V. É. Naidenov; M. M. Markovich (307-309).
N-acetyl derivatives of L-glutamine, L-proline, and 4-hydroxy-L-proline were synthesized in aqueous solutions with acetic anhydride as the acetylating agent. The resulting compounds were used as medicinal substances.
Keywords: α-Amino acids; N-acetyl-L-glutamine; N-acetyl-L-4-hydroxy-L-proline; N-acetyl-L-proline

Use of substituted N,N'-acylbisazoles for the synthesis of ribonucleoside-5'-polyphosphates by Z. P. Belousova; P. P. Purygin; Yu. P. Zarubin (310-313).
A series of N,N'-acylbisazoles were used to synthesize nucleoside-5'-polyphosphates, with target product yields which were 10 – 15% higher than when unsubstituted N,N'-acylbisazoles were used.
Keywords: N,N'-acylbisazoles; substituted; ribonucleoside-5'-polyphosphates; synthesis

Complexes of aminoglycoside antibiotics with copolymers of acrylamide with acrylic and methacrylic acids by M. V. Solovskii; M. Yu. Eropkin; E. M. Eropkina; M. Yu. Smirnova; I. I. Gavrilova (314-318).
Polymer complexes of aminoglycoside antibiotics as bases with low molecular weight water-soluble copolymers of acrylamide (ACR) with acrylic (AA) and methacrylic (MA) acids containing 15 – 20 mol% carboxyl groups were synthesized. Complexes of antibiotics with ACR-MA copolymers were found to be more stable in aqueous and aqueous salt solutions and to have less toxicity in vitro than complexes based on ACR-AA copolymers. All polymer complexes retained high levels of antibacterial activity.
Keywords: Polymer complexes; aminoglycoside antibiotics; acrylamide copolymers; acrylic and methacrylic acids; in vitro toxicity; antimicrobial activity

New interpolyelectrolyte complexes (IPEC) between oppositely charged types of Eudragit®, EPO and L100-55, with different molar ratios were synthesized with the aim of seeking potential carriers for oral delivery systems. Elemental analysis showed that the resulting polycomplexes had different compositions, with 0.36 < Z = [EPO]/[L100] < 1.81. The structural properties of the materials assessed by IR spectroscopy and modulated-temperature differential scanning calorimetry showed that all IPEC were stabilized by a cooperative system of ionic bonds, were chemically homogeneous, and were characterized by the presence of a single glass transition temperature. These properties suggest that the polycomplexes synthesized here have potential for further study as carriers for controlled drug release in specified parts of the gastrointestinal tract.
Keywords: Eudragit® EPO and L100-55; interpolyelectrolyte complexes; synthesis; physicochemical properties

Studies of the process of tablet coating by E. V. Flisyuk (324-327).
The application of coatings to tablets is considiered as a complex process with a number of side effects. We present here the results of theoretical and experimental studies of the application of film coatings to tablets in fluidized bed and drum coater devices. Identification of the optimum conditions for applying the correct quantity of coating to tablets should take account of all effects accompanying this process.
Keywords: Application of coatings; tablets; fluidized bed; coater; heat and mass transfer; tablet defects

Identification of endogenous and exogenous glucocorticoids by HPLC-MS in human urine by M. A. Dikunets; S. A. Appolonova; G. M. Rodchenkov (328-333).
A selective and sensitive screening method for identifying 20 endogenous and exogenous corticosteroids in human urine is presented. Analysis was performed by HPLC with a mass-selective “ion trap” detector and spray ionization. Urine samples were prepared by liquid-liquid extraction (with a mixture of toluene and di-ethyl ether, 50:50 v/v). The dry residue was redissolved in 50 μl of methanol and aliquots of 5 μl were loaded onto the HPLC-MS system. Chromatographic separation was performed on a Restek Ultra C18 (2.1 × 100 mm, 5 μm) column. The mobile phase was a solution of 0.05% formic acid containing 20 mM ammonium acetate pH 3 (A) and acetonitrile (B). The detection limits for all corticosteroids were 1 – 3 ng/ml. Chromatographic separation and mass spectrometric data for identification of mixtures of steric isomers of betamethasone and dexamethasone are presented.
Keywords: HPLC-MS; corticosteroids; doping control

Recent years have seen increasing use of formulations containing sets of compensatory metabolites in the form of short-chain fatty acids (SCFA), i.e., acetic, propionic, butyric, isobutyric, valeric, and isovaleric acids. This has led to the need to adapt existing analytical methods to monitor the presence of SCFA in probiotic formulations. The main task of the present study was to develop an assay for SCFA in formulations based on bacterial substrates. This was addressed using gas chromatography with flame ionization detection.
Keywords: GC (gas chromatography); probiotics; short-chain fatty acids

Qualitative and quantitative analysis of a new lyophilized liposomal formulation of photodithazine by Tran Thi Hai Yen; E. V. Ignat’eva; A. P. Polozkova; G. V. Ramenskaya; N. A. Oborotova (337-340).
Photodithazine, a second-generation photosensitizer, is used in the photodynamic therapy of tumors. With the aims of improving the selectivity of its accumulation in tumor tissue and increasing its stability on storage, studies at the N. N. Blokhin Russian Oncological Scientific Center, Russian Academy of Medical Sciences, led to the creation of a new liposomal formulation of Photodithazine, “Liposomal Photodithazine, lyophilisate for preparation of solution for injection 1.5 mg.” We report here the development of a method for identifying egg phosphatidylcholine and Photodithazine and a method for assaying Photodithazine contents in the new lyophilized liposomal formulation.
Keywords: Photodithazine; liposomes; qualitative analysis; quantitative assay; spectrophotometry; thin layer chromatography