Pharmaceutical Chemistry Journal (v.41, #9)

Principles of magnetohydrodynamic thermochemotherapy of malignant tumors (A review) by N. A. Brusentsov; T. N. Brusentsova; E. Yu. Filinova (455-460).
New experimental and clinical data on the hyperthermia of malignant tumors are reviewed. The molecular biology mechanisms and principles of the magnetohydrodynamic thermochemotherapy (MHTCT) of tumors are considered. Attempts at automation of the MHTCT process using magnetically driven antitumor nanopreparations with low Curie temperatures are discussed.

Evaluating cycvalon activity under conditions of chronic endotoxicosis models in rats by A. V. Simonyan; V. V. Novochadov; M. A. Simonyan; A. N. Goryachev (461-463).
Using the results of instrumental and numerical investigations of structure — activity relationships among derivatives and structural analogs of cinnamic acid, we predicted and then experimentally proved the protective action of the new bile-expelling drug cycvalon (a cyclohexanone derivative) in rats under the conditions of model endotoxicosis. The drug effectively prevented cytotoxic damage of liver and kidney tissues related to the vascular and fibroplastic mechanisms. At the same time, cycvalon is of low effectiveness with respect to the development of lung tissue damage, chronic pneumonia, and pneumofibrosis.

The effect of the new amino acid preparation tavamin on the free amino acid pool in heart has been studied under alcohol withdrawal syndrome (AWS) conditions in rats. The AWS in rats alcoholized according to Majchrowicz and Hunt leads to a pronounced dysbalance in the pool of free amino acids. It is established that tavamin is capable of normalizing the pool of free amino acids in rat heart against the AWS background.

Synthesis and anticonvulsant activity of pyrano[4′,3′:4,5]pyrido[2,3-b]thieno[3,2-d] pyrimidine derivatives and pyrimido[5′,4′:2,3]-thieno[2,3-c]isoquinoline derivatives by E. G. Paronikyan; A. S. Noravyan; Sh. F. Akopyan; I. A. Dzhagatspanyan; I. M. Nazaryan; R. G. Paronikyan (466-469).
Methods for the synthesis of condensed thieno[3,2-d]pyrimidines based on pyrano[4,3-d]thieno[2,3-b]pyridines and thieno[2,3-b]isoquinolines have been developed and a series of new derivatives have been synthesized. The anticonvulsant activity of the synthesized compounds has been studied. Several compounds possessing specific anticonvulsant activity with respect to corazole-induced convulsions are revealed.

Several 4-substituted 1,3,5-triazino[1,2-a]benzimidazol-2-amines were prepared via cyclization of 2-benzimidazolylguanidine with various reactants. The prototropic tautomerism in the obtained dihydro analogs was investigated. According to the NMR data, the 3,4-dihydro form was found to predominate in DMSO solutions. All tested compounds inhibited the activity of mammalian dihydrofolate reductase. The most active compound was 4,4-dimethyl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazol-2-amine (IC50 = 10.9 mM).

Synthesis and antioxidant activity of azomethines by E. F. Magomedova; V. V. Pinyaskin; A. Sh. Aminova (474-475).
Four new azomethines have been synthesized. Quantum-chemical calculations of the atomic electron density distribution in the synthesized and known azomethines have been carried out. Their antioxidant activity has been studied in a model system with linolenic acid as the substrate. It is established that the electron density on the carbon atom of azomethine group is correlated with the antioxidant activity in the series of azomethines containing NO2 groups in their structures.

Synthesis and biological activity of 4-acyl-5-aryl-3-hydroxy-1-(2-hydroxyethylaminoethyl)-3-pyrrolin-2-ones by V. L. Gein; N. N. Kasimova; A. L. Moiseev; M. A. Sheptukha; B. Ya. Syropyatov; N. G. Ismailova; E. V. Voronina; O. I. Ivanenko (476-479).
A series of 4-acyl-5-aryl-3-hydroxy-1-(2-hydroxyethylaminoethyl)-3-pyrrolin-2-ones (I) and their hydrochlorides (II) were synthesized via reactions of methyl esters of acylpyruvic acids with a mixture of aromatic aldehyde and N-hydroxyethylethylenediamine. The antibacterial activity of compounds I and the influence of compounds I and II on blood coagulation were studied. All compounds demonstrate pronounced anticoagulant or hemostatic action.

Synthesis and antifungal activity of organofluorine derivatives of levorin by V. V. Belakhov; Yu. D. Shenin; R. A. Araviisky (480-482).
Reactions of the polyene macrolide antibiotic levorin with organofluorine alcohols lead to the formation of organofluorine esters. Two organofluorine derivatives of levorin have been synthesized and their physicochemical and biological properties have been studied. These derivatives show high antifungal activity against a large number of test cultures. The acute toxicity (LD50) of levorin derivatives was about half that of the initial antibiotic.

Synthesis and antimicrobial activity of substituted amides and hydrazides of N-acyl-5-bromanthranilic acids by K. V. Andryukov; M. V. Tomilov; L. M. Korkodinova; T. F. Odegova (483-485).
A series of 17 new substituted amides and hydrazides of N-acyl-5-bromanthranilic acids were synthesized. The antimicrobial activity of these compounds with respect to St. aureus and E. coli was evaluated. It was found that of N-chloracetyl-5-bromanthranlic acid methylamide and hydrazide significantly suppressed the growth of test microbes, with a minimum inhibitory concentration of 15.6 mg/ml against St. aureus and 15.6–31.5 mg/ml against E. coli. The other tested compounds were significantly less active.

À preclinical study of the safety of silymar, a new phytopreparation from Saint-Mary thistle (Silybum marianum) fruits possessing hepatoprotector properties, has been carried out. The parent substance exhibited low general toxicity upon a single intragastric or intraperitoneal administration in both male and female rats and mice. The intragastric administration of silymar in rats for one month in a dose of 20, 200, and 2000 mg/kg showed evidence of a low chronic toxicity. Intragastric administration of silymar (0.1-g ready-to-use tablets) in dogs for three months in a dose of 100 mg/kg did not produce any significant changes of the heart, liver, kidneys, blood, and nervous system of the animals as indicated by the results of hematological, biochemical, and functional tests. As for specific toxicity manifestations, the intragastric administration of silymar in guinea pigs for one month in a dose of 10 and 50 mg/kg can lead to immediate allergic reactions.

Isolation and biological activity of lipids from licorice (Glycyrrhiza glabra) roots by S. B. Denisova; V. T. Danilov; S. G. Yunusova; V. A. Davydova; Yu. I. Murinov; F. S. Zarudii (489-491).
Hexane extract of licorice (Glycyrrhiza glabra L.) roots was obtained and investigated. Hydrocarbons, sterol ethers, triacylglycerides, free fatty acids, and free sterols were identified. The extract contains 70% neutral and 30% polar lipids. It is established that the lipid fraction of licorice roots is more effective than the analogous fraction of rosehip oil in stimulating the reparative regeneration of skin. In addition, this fraction also exhibits pronounced antiinflammatory and antiulcer effects, while being virtually nontoxic. Based on these results, the lipid fraction of licorice roots can be recommended as a parent substance for creating effective preparations in various medicinal forms.

A series of plants of the Amaryllidaceae family (Galanthus woronowii A. Los., Galanthus krasnowii Hohrjakov, Galanthus caucasicus Bacer A. Grossheim, Galanthus latifolius Wor, Leucojum aestivum L., Stenbergia colchiciflora Waldst et Kit, Pancratium maritimum L., Crinum giganteum L., Narcissus tazetta L.), grown and introduced in Georgia, has been studied for their alkaloid composition. Alkaloids galanthamine, lycorine, tazettine, galanthine, galanthusine, demethylhomolycorine, and gemanthamine have been isolated and chemically characterized. The dynamics of galanthamine accumulation during vegetation has been studied. It is established that the content of galanthamine reaches maximum in bulbs at the end of the vegetation stage (except for L. aestivum, in which the maximum is reached at the beginning of vegetation). The bulbs should be harvested in the indicated vegetation periods. The plants of G. woronowii, G. krasnowii, N. tazetta, and L. aestivum species are recommended as raw materials for obtaining galanthamine hydrobromide.

A series of thio-5-nitropyrimidine (thio-5-NP) derivatives was synthesized using the reactions of chlorine-substituted 5-NPs with various aromatic and boron-containing thiols. Reactions of 4,6-dithio-5-NP derivatives with nucleophiles were studied. Stable 2-σ-adducts were obtained using a boron-containing 4,6-dithio-5-NP derivative. The interaction of an aromatic sulfide of 5-NP with 1-phenyl-3-methylpyrazol-5-one led to substitution at one of the arylthio groups. The NMR and mass spectra of the synthesized compounds were obtained; the 2-oxy-σ-adduct was characterized by x-ray diffraction.

A new approach to the laboratory synthesis of magnetite has been developed, which differs from the well-known methods in the chemical reaction scheme, the amounts of initial reactants, and the precipitant. The results of x-ray diffraction, thermoanalytical measurements, and IR spectroscopic analysis showed the identity of the products obtained using the proposed method and the other methods described in the literature.

Biopharmaceutical investigations of biodegradable medicinal films containing anilocaine by I. V. Alekseeva; T. E. Ryumina; V. I. Pantsurkin; T. F. Odegova (504-507).
The results of technological and biopharmaceutical investigations of the domestic local anesthetic anilocaine (possessing significant surface anesthetic, antiinflammatory, and moderate antimicrobial properties) were used to develop compositions of new promising multifunctional medicinal forms, including biodegradable films for the treatment of disorders in the maxillofacial area.

Network copolymers of acrylic and methacrylic acids: Hydrophilic ointment bases for wound-healing preparations by E. M. Tazhbaev; R. N. Pak; S. B. Akhmetova; M. Zh. Burkeev; A. E. Gulyaev; S. M. Adekenov (508-511).
Investigations aimed at the development of a combined wound-healing preparation on a hydrophilic ointment base have been carried out. Copolymers of acrylic acid and its derivatives with a new divinyl monomer, β-vinyloxyethylamide of acrylic acid, are proposed as the bases. It is established that these ointment bases exhibit sufficiently high osmotic activity. Polymer-based complexes including the ethereal oil of smooth wormwood and the proteolytic enzyme protosubtilin showed pronounced antibacterial and wound-healing activity.