Pharmaceutical Chemistry Journal (v.42, #4)

Magnetohydrodynamic thermochemotherapy of malignant tumors with nanopreparations with magnetic resonance monitoring by N. A. Brusentsov; T. N. Brusentsova; E. Yu. Filinova; Yu. A. Pirogov; D. A. Kupriyanov; A. I. Dubina; M. N. Shumskikh; L. I. Shumakov; N. Ya. Yurchenko; E. A. Anashkina; A. A. Shevelev (157-164).
Intravenous administration of dextran-ferrite sol was used to amplify T2-weighed echo gradient (500/15) scanning MR images with visualization of the invasion margins of tumor cells into healthy tissues, along with macro-and micrometastases, in animals with lymphocytic leukemia and Ehrlich and Lewis carcinomas. Magnetohydrodynamic thermochemotherapy (MTCT) using a cyclophosphamide-containing magnetic fluid (saturation magnetization (Ms) 8.6 kA/m, pH 7.4, ζ + 13 mV) at 46°C for 30 min in an alternating magnetic field (0.88 MHz, 7.2 kA/m, 0.15 kW) with aspiration of necrotic material (ANM) produced regression of P388 tumors of volume ∼110 mm3 in BDF1 mice prior to metastasis by 40%, with an increase in lifetime (ILT) of 310%; in tumors of volume ∼330 mm3 after metastasis and MTCT-ANM with cyclophosphamide pretreatment, ILT was 220%.

Synthesis and mutagenic activity of the hydrochlorides of S-(2-alkoxy-5-acetylbenzyl)isothioureas and 3-substituted aminomethyl-4-alkoxyacetophenones by M. A. Kaldrikyan; A. V. Khekoyan; L. A. Grigoryan; G. M. Paronikyan; G. A. Dabrinyan (165-168).
The interaction of 2-alkoxy-5-acetylbenzylchlorides with thiourea and secondary amines was used to prepare the corresponding hydrochlorides of S-(2-alkoxy-5-acetylbenzyl)isothioureas and 3-substituted aminomethylacetophenones. These latter were converted into their hydrochloride salts. Compounds with high mutagenic activity were identified.

Synthesis and tuberculostatic activity of fluorine-containing derivatives of quinolone, quinazolinone, and benzothiazinone by É. V. Nosova; G. N. Liponova; M. A. Kravchenko; A. A. Laeva; V. N. Charushin (169-174).
Methods for the synthesis of fluorine-containing derivatives of quinolones, quinazolinones, and benzothiazinones based on the interaction of polyfluorobenzoic acid chloranhydrides with N,N-N,C-, and N,S-dinucleophiles are described. Use of (tetrafluorobenzoyl)isothiocyanate as the fluorine-containing block provides extensive opportunities for the synthesis of 2-substituted benzothiazinones. Some of the fluorine-containing azaheterocyclic compounds synthesized here had moderate and high activity against Mycobacterium tuberculosis H37Rv.

Synthesis and antiaggregation activity of 1-adamantoylaminopyridines by V. A. Ermokhin; N. A. Klenova; P. P. Purygin (175-176).
Adamantoylated aminopyridines were synthesized by reaction of 1-adamantoylchloride with the corresponding aminopyridines. Decreases in serotonin-induced platelet aggregation were seen in the presence of N-(1-adamantoyl)-3-aminopyridine and N-(1-adamantoyl)-2-aminopyridine.

Synthesis of 2-(3-spiro-cyclohexyl-3,4-dihydroisoquinolyl-1)acetic acid derivatives and their effects on blood clotting by A. G. Mikhailovskii; N. N. Polygalova; N. G. Ismailova; B. Ya. Syropyatov; M. I. Vakhrin (177-179).
Cyclocondensation of the esters and amides of cyanoacetic acid with 1-spiro-cyclohexylcarbinols yielded derivatives of 2-(3-spiro-cyclohexyl-3,4-dihydroisoquinolyl-1)acetic acid containing and not containing methylenedioxo groups at positions 6,7. Compounds containing this group were found to increase blood clotting; those without it, conversely, decreased clotting. The most active compounds had effects comparable to those of ethamsylate and heparin.

Synthesis and antifungal and antibacterial activity of hexahydronicotine derivatives by A. D. Kagarlitskii; L. A. Krichevskii; Z. M. Astaf’eva; S. B. Akhmetova; R. B. Seidakhmetova; A. I. Drab (180-182).
Acylation of hexahydronicotine with anhydrides of dicarboxylic acids yielded amido acids. Reaction of amido acids with amines, ethanol, and hydrazine produced derivatives. Studies of these compounds showed them to have antifungal and antibacterial activity.

Fungicidal and toxicological properties of functionally substituted nitrobenzofuroxanes by L. M. Yusupova; S. Yu. Garmonov; I. M. Zakharov; A. R. Bykov; I. F. Falyakhov; T. V. Garipov (183-185).
The fungicidal activities of 5-nitro-4,6-dichlorobenzofuroxane, 4,6-dinitro-5,7-dichlorobenzofuroxane, and a mixture of these two compounds were studied. The main toxicological characteristics of biologically active functionally substituted nitrobenzofuroxanes were identified.

Molecular modeling of the three-dimensional structure of the extracellular loops of the CCK2 receptor and their binding with the CCK-4 tetrapeptide by P. E. Kuznetsov; N. B. Kuznetsova; S. V. Shul’gin; A. V. Shantrokha; E. N. Dubas (186-190).
Molecular modeling methods were used, along with partial experimental data, to identify the equilibrium conformation of the first and second extracellular loops of the cholecystokinin-2 receptor. A model of the spatial structure of a fragment of the active center of the CCK2 receptor, consisting of three extracellular loops, with the ligand, i.e., the tetrapeptide CCK-4 was constructed. This model was used to evaluate the mechanism of the ligand-receptor interaction. Molecular modeling demonstrated the possibility of simultaneous transfer of a proton and electron density from the CCK-4 ligand to amino acids of the CCK2 receptor. This model of the ligand-receptor interaction may provide a tool for predicting the pharmacological profiles of series of CCK-4 analogs.

Synthesis and antibacterial activity of some new 1-aroyl-3-(substituted-2-benzothiazolyl)thioureas by Aamer Saeed; Hummera Rafique; A. Hameed; S. Rasheed (191-195).
An efficient, synthesis of some new 1-aroyl-3-(substituted-2-benzothiazolyl)-thioureas is reported. Substituted anilines were treated with potassium thiocyanate and bromine in acidic medium to afford the corresponding 2-amino-benzothiazoles (2a–e). Treatment of the latter with suitably substituted aroyl isocyanates, produced in situ by reaction of corresponding aroyl chlorides with thiocyanate in acetone, afforded the 1-aroyl-3-(substituted-2-benzothiazolyl)thioureas (3a–k). The structures were confirmed by physical, IR, NMR, and mass spectral data. The synthesized compounds (2a–d, 3a–k) were assayed in vitro for their antimicrobial activity against Gram positive and Gram negative bacteria and were found to exhibit moderate to potent activity towards the tested microorganisms, as compared to the standard drugs.

Complexes of the type [M(dssdh)]Cl and [M(dbsdh)Cl]Cl, where M = Co(II), Ni(II), Cu(II), Zn(II), and Cd(II), Hdssdh = diacetylsalicylaldehyde succinic acid dihydrazone, and dbsdh = diacetylbenzaldehyde succinic acid dihydrazone, have been prepared and characterized by elemental analyses, magnetic moments, molar conductance, and electronic, ESR, infrared, and X-ray diffraction studies. The complexes are stable solids and are 1:1 electrolytes. Magnetic moments and electronic spectral studies suggest a spin-free octahedral geometry for all the complexes. ESR spectra of Cu(II) complexes indicate the d x 2-y 2 ground state and a tetragonally distorted octahedral geometry for the metal. IR spectra show the monobasic hexadentate nature of the ligand Hdssdh coordinating to the metal ion via three >C=O, two >C=N-, and a deprotonated phenolate group, whereas the neutral pentadentate dbsdh ligand bonds through three >C=O and two >C=N-groups. X-ray powder diffraction parameters for some of the complexes correspond to an orthorhombic crystal lattice. The complexes show appreciable antifungal activity against Alternaria sp., Curvularia sp., and Pseudocercospora sp. and fair antibacterial activity against Pseudomonas fluorescence and Clostridium thermocellum bacteria.

Studies of the essential oil of Dracocephalum moldavica cultivated in the Stavropol region by A. S. Nikitina; O. I. Popova; L. S. Ushakova; V. V. Chumakova; L. I. Ivanova (203-207).
An essential oil was extracted from the above-ground part of breeding specimens of the Moldavian dragon’s head. The quantitative composition of the essential oil (0.10–0.43%) was studied and the dynamics of its accumulation in different plant organs were determined on introduction into the Stavropol region. The conditions for quantitative estimation of the essential oil content by distillation were optimized. Variability of the mass proportion in plant organs and in the quantitative ratios in samples of raw material during the mass flowering period was studied. The resulting experimental data provide grounds for the correct selection of the optimum height at which to cut plants on harvesting. The stock material (herb) should contain inflorescences, leaves, and no more than 30% stems, as these have the lowest essential oil content. The optimal height for cutting plants is 35–40 cm. Analysis of the essential oil by gas-liquid chromatography showed that it contained up to 36 components, the dominant of which was citral. Terpineol, linalool, limonene, acyclic monoterpenoids (geranyl acetate, nerol, linalyl acetate, geranyl acetate, and geraniol) were present in significant quantities in samples of the essential oil, amounting to about 35%.

A method for the quantitative estimation of the total flavonoid fraction in greater plantain leaves was developed; the method had a relative error of no greater than 4%. Metrological analysis showed that the method was accurate and reproducible. Greater plantain leaf flavonoid contents, expressed as baicalin, were 2.12–3.45%.

Development of a new xymedone production technology by P. G. Belyaev; G. Kh. Khisamutdinov; S. G. Sharypova; V. P. Konovalova; I. Z. Kondyukov; S. I. Valeshnii; S. P. Smirnov; V. P. Il’in (211-214).
A new technology for preparing substance used in the burn treatment agent xymedone by interaction of ethanolurea with acetyl acetate in isopropanol medium in the presence of hydrochloric acid and subsequent neutralization of the resulting xymedone HCl with ammonia or alkaline solution is described. This technology was introduced into experimental production at the Federal State Unitary Science Research Institute “Kristall.”

Compatibility studies between piroxicam and pharmaceutical excipients used in solid dosage forms by H. K. Stulzer; M. P. Tagliari; A. P. Cruz; M. A. S. Silva; M. C. M. Laranjeira (215-219).
Differential scanning calorimetry (DSC) with the support of Fourier transform infrared spectroscopy (FT-IR) was used as a screening technique for testing the compatibility of piroxicam (4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3carboxamide-1,1-dioxide) with various pharmaceutical excipients for solid dosage forms. Based on the results, magnesium stearate, stearic acid, and mannitol were found to show interaction with piroxicam. In conclusion, tools of DSC and FT-IR were successfully employed to evaluate the compatibility of piroxicam and selected excipients.

Flow-injection estimation of 2-aminophenol in pharmaceutical agents using piezoquartz immunosensors by E. S. Dergunova; O. V. Voronezhtseva; S. A. Eremin; T. N. Ermolaeva (220-223).
A flow piezoquartz immunosensor was developed for the rapid estimation of 4-aminophenol in pharmaceutical formulations based on paracetamol. The bioreceptor coating was a 4-aminophenol-protein conjugate (4-AP-GA-BSA), immobilized on the silanized surface of a silver electrode. The effects of the concentration of polyclonal antibodies on the analytical signal of the sensor were studied: the activities of immunological reagents were assessed in terms of the binding constant K b. A method for flow-injection estimation of 4-aminophenol in pharmaceutical formulations using the piezoquartz immunosensor as the detector was developed. The calibration curve was linear over the concentration range 2–120 ng/ml and the detection limit for 4-aminophenol was 1.1 ng/ml.

Estimation of cationic surfactants in medicinal formulations by N. M. Mikhaleva; E. G. Kulapina; O. V. Mikhaleva (224-227).
A method for estimating cationic surfactants in various surfactant-containing medicinal formulations for medical use (Calgel, Chlorhexidine, Hexicon, Psylo-Balsam, Nittifor) was developed. The method uses a potentiometric sensor based on cetylpyridinium dodecylsulfate.

Preparative flow thin-layer chromatography of biomembrane higher fatty acid diglycerides by V. D. Tsydendambaev; V. P. Pchelkin; A. G. Vereshchagin (228-231).
Preparative separation of positional isomers of diglycerides (DG) in silica gel layers was performed using a horizontal flow chamber. The time at which dynamic equilibrium between the solid, liquid, and gas phases was established in this chamber was identified using organic stains. In order for this equilibrium to be established, the chloroform flow had to be passed through the adsorbent layer for about 4 h. Layers stabilized by this method were used to fractionate mixtures of rac-1,3-and rac-1,2-DG (17.65 mg) obtained by transesterification of triglycerides from plant oils and loaded onto the carrier layer at the start concentrating zone of the plate using a sample applicator. The yield of this mixture after extraction from sorbent was 16.88 ± 0.77 mg (95.6 ± 4.4%) and the ratio of rac-1,3-to rac-1,2-DG was 0.76 ± 0.02.