Pharmaceutical Chemistry Journal (v.45, #5)

Synthesis and antiviral activity of functionally substituted indole-3-acetic acids by A. V. Ivashchenko; P. M. Yamanushkin; O. D. Mit’kin; I. A. Leneva; I. T. Fedyakina (261-266).
Methods for the synthesis of dibromo-substituted derivatives of indomethacin and related N-alkylated indole-3-acetic acid derivatives have been developed. Pathways for the introduction of various substituents, in particular nitrogen-containing groups, into the structure of auxins have been studied. The antiviral activity of some brominated functionally substituted compounds with respect to A/Aichi/2/69 influenza virus in MDCK cell culture and an influenza pneumonia model in mice has been evaluated.
Keywords: synthesis; indole-3-acetic acid (auxin); indomethacin; bromination

Synthesis and antiviral activity of several quinoline derivatives by M. N. Zemtsova; A. V. Zimichev; P. L. Trakhtenberg; Yu. N. Klimochkin; M. V. Leonova; S. M. Balakhnin; N. I. Bormotov; O. A. Serova; E. F. Belanov (267-269).
The antiviral activity of 2-substituted and 2,6-disubstituted quinoline-4-carboxylic acids and their derivatives has been studied against orthopoxviruses on Vero and MK-2 cell cultures. High activity has been found for 2-(1,1′-biphenyl-4-yl)quinoline-4-carboxylic acid.
Keywords: quinolinecarboxylic acids; acid derivatives; biological activity

Synthesis and antiaggregant activity of 2-cycloalkylamino-5-thienyl- and -5-furyl-6H-1,3,4-thiadiazines by O. N. Chupakhin; L. P. Sidorova; N. M. Perova; V. L. Rusinov; T. M. Vasil’eva; V. A. Makarov (270-274).
A series of new 5-(thienyl-2)-, 5-(furyl-2)-, and 5-(thienyl-3)-1,3,4-thiadiazine derivatives have been synthesized using methods based on the cyclocondensation of α-bromoacetylthiophenes or α-bromo-2-acetylfurans with 4-substituted thiosemicarbazides. The effects of the synthesized compounds on human platelet aggregation in vitro and on rabbit platelet aggregation ex vivo have been studied. The most active 5-(thienyl-2)-1,3,4-thiadiazines inhibit human platelet aggregation induced by ADP and arachidonic acid in a broad concentration range. These compounds have good potential as emergency drugs for the treatment and prophylaxis of infarction and stroke.
Keywords: synthesis; 1,3,4-thiadiazines; platelet aggregation

Synthesis and hypoglycemic and anti-inflammatory activity of metal complexes of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid N-heterylamides by N. A. Pulina; F. V. Sobin; A. I. Krasnova; T. A. Yushkova; V. V. Yushkov; P. A. Mokin; K. V. Yatsenko; E. B. Babushkina (275-278).
The reaction of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid N-heterylamides with dichlorides of manganese, cobalt, and nickel forms the bis[3-aryl-1-(N-heteryl)carboxamido-1, 3-propanedionato] complexes of manganese, cobalt, and nickel, respectively. The hypoglycemic and anti-inflammatory activities of the synthesized compounds and the previously obtained complexes of copper, zinc, and cadmium were investigated. Several highly active substances with two pharmacological effects were found among these products.
Keywords: 4-aryl-2-hydroxy-4-oxo-2-butenoic acid N-heterylamides; metal complexes; hypoglycemic activity; anti-inflammatory activity

Antioxidant activity and flavonoid composition of the new pancreoprotective preparation Pancreophyt by S. M. Nikolaev; I. G. Nikolaeva; Ya. G. Razuvaeva; A. M. Dorzhiev (279-281).
The antioxidant activity of the new pancreoprotective plant preparation Pancreophyt has been studied experimentally on an animal model of acute chloroethane-induced pancreatitis. The flavonoids luteolin-7-glycoside, apigenin, hpyeroside, rutin, vitexin, dihydroquercetin, and quercetin in addition to cinnamic, gallic, caffeic, and cichoric acids were observed in the phytopreparation.
Keywords: antioxidant activity; experimental pancreatitis; plant preparation Pancreophyt; flavonoid composition

Coulometric determination of the free organic acid content in wild-rose fruit by S. G. Abdullina; N. M. Agapova; O. A. Lira; R. Sh. Khaziev; N. P. Kodryanu (282-284).
Anew method based on coulometric titration with potentiometric indication of the titration end point has been developed for the determination of the organic-acid content in wild-rose fruit, cholosas preparation, and wild-rose syrup. The relative error of the coulometric determination of organic acids does not exceed 2%.
Keywords: wild-rose fruit; cholosas; wild-rose syrup; galvanostatic coulometry; electrically generated hydroxide ions; pharmaceuticals analysis

Principles of the combination of chemically complementary grades of Eudragit® copolymers in peroral, matrix, and reservoir types of solid dosage forms with modified release [tablets, microspheres, (micro)pellets] and their manufacturing technology (including film coatings) are considered. Modified drug release is achieved due to the interaction between reactive groups of copolymer pairs, which controls the drug release process both inside matrices and within multilayers or combined coatings. Analysis of these processes has key significance for developing (meth)acrylate polycomplexes, which could be synthesized in both aqueous and organic media, as new classes of drug carriers for constructing modern peroral drug delivery systems.
Keywords: Eudragit® countercharged copolymers; interpolymer complexes; (meth)acrylate polycomplexes; peroral drug delivery systems; controlled release solid dosage forms

The influence of α-amino acid additions on the process of sunflower oil oxidation in oil—water emulsions was investigated. It is established that both amino acids and their salts (hydrochlorides) exhibit an antioxidant effect. The antioxidant action of amino acids increases with an increasing number of nitrogen atoms in the molecule. The amino group is a reactive center at which the process of oil oxidation in the emulsion is inhibited. Amino acids and their salts (hydrochlorides) act on the oil—water interface so as to accelerate the disintegration of lipid peroxide compounds in the water—oil system with the formation of molecular products.
Keywords: antioxidants; amino acids; oxidation; sunflower oil; emulsion

Determining impurity elements in hydroxyapatite by laser mass spectrometry by A. V. Steblevskii; A. S. Berlyand; A. S. Alikhanyan; A. A. Prokopov (299-301).
The method of standard-free laser mass spectrometry was used to determine the quantitative content of impurities”in a synthetic hydroxyapatite. It is established that the content of impurities, in particular, toxic elements such as As, Zn, Pb, and Cr, is very low in the synthesized product. This allows the synthetic hydroxyapatite to be used as a material for intrabone implanatation.
Keywords: hydroxyapatite; laser mass spectrometry; quantitative determination of impurities; intrabone implanatation material

The possibility of applying near-IR spectroscopy for drug quality control with respect to dose uniformity was studied. Methods for the calibration and determination of the content of active ingredients in model drugs with various mass fractions of the active ingredient were developed. Statistical processing of the results showed that both methods give reproducible results and do not introduce systematic errors.
Keywords: pharmaceutical analysis; dose uniformity; near-infrared spectrometry

New approach to detecting counterfeit drugs in tablets by DART mass spectrometry by E. S. Chernetsova; P. O. Bochkov; G. V. Zatonskii; R. A. Abramovich (306-308).
The possibility of using DART mass spectrometry for the identification of active ingredients in tableted drugs has been studied. Analytical results for some drugs such as glycin, nootropyl, anaprilin, mexidol, and biseptol are presented. The benefits and limitations of DART mass spectrometry as applied to fast screening of tableted pharmaceuticals for detecting counterfeits are discussed.
Keywords: DART mass spectrometry; fast screening of pharmaceuticals for counterfeits

Problems related to control of the expiration date of ready-to-use drugs and substances are always timely and can be solved by using differential scanning calorimetry (DSC). This method was used to monitor changes in the concentration of piracetam drug substance during experimental storage. An analysis of the DSC data showed that this technique can be used for determining objectively the expiration date of the drugs irrespective of the storage conditions.
Keywords: piracetam drug substance; stability on storage; differential scanning calorimetry (DSC)

A series of new 3-aryl-4-(6′-aryl-imidazo[2,1-b][1,3,4]thiadiazol-2′-yl-phenylsydnones (16 – 27) were synthesized. The structures of the synthesized compounds were confirmed by the IR, 1H NMR, and mass spectroscopy techniques and elemental analysis. All the newly synthesized compounds were evaluated for their anticancer activity against cervical cancer cell line (Hela) and antimicrobial activity, in particular, antitubercular activity against Mycobacterium tuberculosis (H37Rv).
Keywords: Mesoionic heterocycles; imidazo[2,1-b][1,3,4]thiadiazole; anticancer activity; antimicrobial activity; antitubercular activity

The fresh flowers of Opuntia stricta were collected and extracted with 85% methanol under reflux. The concentrated extract was fractionated with Et2O, EtOAc and petroleum ether. Rhamnetin 3-O-rutinoside was obtained from EtOAc fraction, as confirmed through 1H and 13C NMR, 1H-1H NOESY, 1H-13C HSQC, and mass spectra. The isolated flavonoid glycoside was investigated for its antihyperglycemic activity on alloxan-induced diabetic male albino rats.
Keywords: Opuntia stricta ; flavone; antihyperglycemic activity; albino rats; alloxan-induced diabetes