Pharmaceutical Chemistry Journal (v.44, #2)

Molecular-biological problems of drug design and mechanism of drug action by K. S. Zaikin; G. V. Ramenskaya; A. P. Arzamastsev (51-55).
Keywords: Morphine; tramadol; gas chromatography-mass spectroscopy; blood; pharmacokinetics; pharmacodynamics

Search for new drugs by A. N. Balaev; A. F. Eleev; O. G. Eremin; V. E. Fedorov (56-57).
Five new 1,4-dihydropyridines containing 3-dialkylamino-2,2-dimethylpropyl fragments were synthesized. The hypotensive activity of the resulting compounds was studied.
Keywords: 1,4-dihydropyridine derivatives; antihypertensive activity

Synthesis and antifungal activity of 2-(3,3-dimethyl-1,2,3,4-tetrahydroquinolin-1-idene)-2-oxopropanoic acid amides and hydrazides by O. V. Surikova; A. G. Mikhailovskii; G. A. Aleksandrova; I. N. Kir’yanova; M. I. Vakhrin (58-60).
Reactions with 2,3-dioxopyrrolo[2,1-a]isoquinolines with amines and arylhydrazines were used to synthesize the corresponding amides and hydrazides of 2-oxo-3-(3,3-dimethyl-1,2,3,4-tetrahydroisoquinoline-1-idene)propanoic acid. A number of the resulting compounds were found to have antifungal activity against Candida albicans, the most active being the amide containing a thymol radical, which was active at a concentration of 125 μg/ml.
Keywords: 2,3-Dioxopyrrolo[2,1-a]isoquinolines; reaction with amines and arylhydrazines; 2-oxo-3-(3,3dimethyl-1,2,3,4-tetrahydroisoquinoline-1-idene)propanoic acid amides and hydrazides; antifungal activity against Candida albicans ; maximum effect at a concentration of 125 μg/ml

Synthesis and antimicrobial activity of poly(N-methyl-4-vinylpyridinium triiodide) by M. S. Chernov’yants; I. V. Burykin; R. V. Pisanov; O. A. Shalu (61-63).
Alkylation of poly(4-vinylpyridine) with methyl iodide for 12 h led to synthesis of the anionite poly(N-methyl-4-vinylpyridinium iodide). Iodination of an aqueous solution of the reaction product with an equimolar quantity of iodine in ethanol produced poly(N-methyl-4-vinylpyridinium triiodide) at quantitative yield. The structure of this compound was confirmed by UV, IR, and 1H NMR spectroscopy and potentiometric titration. The antimicrobial activities of the compounds synthesized here are presented.
Keywords: Poly(N-methyl-4-vinylpyridinium iodide); synthesis; antimicrobial activity

Medicinal plants by V. N. Syrov; M. P. Yuldashev; N. V. Tursunova; Z. A. Khushbaktova (64-67).
We report here data on the isolation and chemical structure of lehmanin (a flavonone) and ammothamnidin (a chalcone) from Ammothamnus lehmannii Bunge. Their gastroprotective activities were studied in models of stress-induced ulcers and ulcers induced by reserpine and butadione.
Keywords: Flavonoids; lehmanin; ammothamnidin; quercetin; gastroprotective activity

The structures of pharmacologically active derivatives of the 4-hydroxycoumarin series used therapeutically and for medical hygiene are discussed. It is shown that different structures can be obtained in the crystalline state and in solutions by gradual increases in the distance of the position 3 acyl group of 4-hydroxycoumarin from the aromatic system resulting from the introduction of one or more methylene groups. Tautomeric transformations are discussed, along with the conditions for condensation of these compounds. Reports of the synthesis, purification, pharmacological activity, and mechanisms of action of substances of this medicinal group are presented.
Keywords: Tautomeric transformations; 4-hydroxycoumarin.

Use of nanoparticles to increase the systemic bioavailability of trans-resveratrol by E. A. Oganesyan; I. I. Miroshnichenko; N. S. Vikhrieva; A. A. Lyashenko; S. Yu. Leshkov (74-76).
Resveratrol is a substance of plant origin with antioxidant, anti-inflammatory, and chemoprotective properties used as a biologically active supplement in the prophylaxis of myocardial infarction, types 1 and 2 diabetes, and tumors. The aim of the present work was to develop and perform pharmacokinetic studies of a nanosomal form of resveratrol. The techniques described here yield particles of submicron size, with resveratrol yields of 70–100% and resveratrol contents in lyophilized formulations reaching 15–20%. After oral administration of unmodified resveratrol to mice, only 19% of the dose was taken up into the blood, while use of nanosomal resveratrol formulations based on Eudragit RL and lecithin/chitosan increased bioavailability to 39% and 61% respectively. Increases in the peak plasma resveratrol concentration by factors of 4–5 were also seen in mice given nanoparticles. Thus, conversion of resveratrol to the nanosomal form leads to solubilization and resultant increases in absorption into the bloodstream.
Keywords: Resveratrol; nanoparticles; pharmacokinetics; bioavailability

Studies of the thermal stability of thioacetal by IR spectroscopy by G. N. Bondarenko; S. M. Zenovich (77-80).
The thermal stability of thioacetal—a product of the interaction of acetaldehyde with unithiol (dimercaptopropanesulfonate sodium, DMPS) was studied. Unithiol is a vicinal dithioglycol widely used in medicine for therapeutic purposes. Determination of the limits of the thermal stability of thioacetal allows the methods used for gas-liquid chromatography assay of acetaldehyde contents in biological fluids to be improved. This type of analysis is performed for forensic reasons and with toxicological, diagnostic, and therapeutic aims.
Keywords: Thioacetal; acetaldehyde; unithiol; thermal stability

Effects of modification of highly disperse silica with polyvinylpyrollidone on gelatin adsorption by A. P. Vasilenko; N. V. Guzenko; L. V. Nosach; E. F. Voronin (81-84).
The effects of surface modification of highly disperse silica with polyvinylpyrrolidone on its ability to adsorb gelatin were studied. This modification was found to produce a monotonic decrease in the proteopectic properties of silica resulting from changes in the nature of surface active centers. Changes in other pharmacologically important properties, i.e., rheological and hemolytic, resulting from modification of silica with polyvinylpyrrolidone, were extreme in nature. Thus modification produced strongly positive effects with minimal protein adsorption, indicating that PVP can be used as a modifier for creating new medicinal formulations based on highly disperse silica. The optimum level of modification of silica with polyvinylpyrrolidone was 20–30 mg/g, corresponding to about 15% of monolayer capacity.
Keywords: Highly disperse silica; Silix; adsorption modification; polyvinylpyrrolidone; gelatin adsorption

A method of comminuting natural zeolite for the production of biologically active additives by K. S. Golokhvast; A. M. Panichev; I. Yu. Chekryzhov; M. I. Kusaikin (85-88).
This article describes a method of grinding a solid mineral material (zeolite), which can be used in medical applications, for the preparation of starting components for biologically active additives. Our method of preparing a solid natural material includes mechanical grinding, ultrasound comminution, and grading of natural zeolite. It differs from previously described methods in that material already ground mechanically to particle sizes of 5–20 mm is subjected to comminution and this process continues until particles of 1–2 to 10 μm are obtained. Zeolite particles obtained after processing in the homogenizer have greater roundness and smaller sizes than those obtained by mechanical crushing. Furthermore, our ultrasound method of comminuting zeolites also reduces the comminution process time by factors of 1.5–12.
Keywords: Zeolites; ultrasound comminution; clinoptilolite

Studies of moisture exchange between stearic acid, calcium stearate, and magnesium stearate by V. A. Dubinsksaya; N. A. Polyakov; Yu. L. Suponitskii; N. N. Dement’eva; V. A. Bykov (89-93).
Moisture content, hygroscopicity, and thermal desorption parameters of stearic acid, calcium stearate, and magnesium stearate, which are used as excipients for tableting, were studied. In contrast to stearic acid, calcium and magnesium stearates were found to be hygroscopic compounds which were able to absorb moisture in conditions of elevated air moisture content, this water being present in the bound and free states. Moisture was eliminated at temperatures of 40–105°C. Depending on the manufacturer, excipient samples differed in terms of moisture content and sorptive capacity, demonstrating the importance of studying these parameters. Endothermic effects for calcium stearate (T max = 125.7°C) and magnesium stearate (T max = 113°C) were induced by melting of the crystalline structure of these compounds and their transition to the amorphous state.
Keywords: Moisture and thermodynamic parameters; stearic acid; calcium stearate; magnesium stearate

Design, synthesis and antimicrobial study of some pyrimidine derivatives by Dharmendra H. Patel; Kishor H. Chikhalia; Nisha K. Shah; Dhaval P. Patel; Pankaj B. Kaswala; Vipul M. Buha (94-98).
A series of 4-[4-(2, 4-dichloro-5-fluorophenyl)-6-(4-methoxyphenyl)pyrimidine-2-yl]-1-(arylaminocarbonyl/thiocarbonyl)semicarbazides was synthesized and their in vitro antibacterial activity was studied.
Keywords: Chalcone; Pyrimidine; Antimicrobial activity; MIC

Analysis of thyrostatic heteroaromatic thioamides (review) by A. O. Dolinkin; M. S. Chernov’yants (99-106).
This review discusses methods widely used in pharmaceutical and clinical practice for the identification and assay of the thyrostatic agents imidazoline-2-thione and uracil-2-thiones. Sample preparation stages (solid-phase and liquid extraction from biological materials) are discussed, along with chemical modification of drug molecules. Ascheme for a hypothetical model of the inhibitory action of thyrostatic agents on thyroid hormone biosynthesis is presented. The analytical characteristics of individual methods for assaying thyrostatic agents discussed in this review can be used in manufacturing at the quality control stage.
Keywords: Heteroaromatic thiones; imidazole and uracil derivatives; hypothetical model of antithyroid action; volt-amperometric and titrimetric assay methods; chemical modification

Planar chromatography in studies of optically active drugs by V. P. Pakhomov; O. A. Checha (107-109).
The use of planar chromatography for the investigation and separation of optically active drugs into individual stereoisomers with subsequent identification of isomers was demonstrated using amino acids and amlodipine besylate as examples.
Keywords: Optically active drugs; amino acids; amlodipine besylate; planar chromatography