Pharmaceutical Chemistry Journal (v.44, #9)

Synthesis and pharmacological properties of alkylammonium salts of N,N′-malonyl-bis-p-aminobenzoic acid by F. G. Shepel’; R. N. Zozulya; D. F. Shepel’; F. Z. Makaev (469-471).
A series of ammonium salts of N,N′-malonyl-bis-p-aminobenzoic acid with some alkylamines have been obtained. It is established that these compounds possess hypotensive, antiarrhythmic, and anticoagulative activities depending on the structure of the alkylamine constituents.
Keywords: ammonium salts of N,N′-malonyl-bis-p-aminobenzoic acid; synthesis; hypotensive effect; antiarrhythmic activity

Synthesis and antiserotoninergic activity of new tropane derivatives by L. M. Kostochka; T. S. Gan’shina; R. S. Mirzoyan; S. B. Seredenin (472-475).
Tropane derivatives have been synthesized with the aim of finding serotonin antagonists with potential antimigraine activity. Aromatic and heteroaromatic esters of tropan-3-oxime were obtained. Their cerebrovascular activity as manifested by antiserotonin properties has been studied. On this basis the new antimigraine drug tropoxin has been discovered.
Keywords: tropane; tropoxin; serotonin; anitmigraine activity

Synthesis and pharmacological activity of 3-carboxypicolinic acid amides by M. E. Kon’shin; B. Ya. Syropyatov; M. I. Vakhrin; P. G. Neifel’d; V. P. Feshin; S. N. Shurov; T. F. Odegova (476-479).
A series of substituted amides of 3-carboxypicolinic acid have been synthesized via the interaction of quinolinic acid anhydride with alkyl(aryl)amines. Their structures were studied by 1H and 13C NMR spectroscopy. The direction of the reaction was explained by quantum-chemistry methods. Three compounds demonstrated hemostatic activity. Two substances exhibited anticoagulant properties. Most substances also exhibited weak bacteriostatic activity.
Keywords: 3-carboxypicolinic acid amides; synthesis; hemostatic activity; anticoagulant properties.

It is established that 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones react with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines with the formation of (1Z,3Z)-4-aryl-4-hydroxy-1-(3,3-dialkyl-3,4-dihydroisoquinoline1(2H)-ylidene)-but-3-en-4-ones. The synthesized compounds were tested for anti-inflammatory and analgesic properties.
Keywords: dioxinones; 1-methyl-3,4-dihydroisoquinolines; analgesic activity; anti-inflammatory activity

Synthesis and analgesic activity of 4-aroyl-1H-benzo[c]oxepin-3-ones by A. A. Glukhov; N. F. Kirillov; A. A. Potapova; R. R. Makhmudov; L. G. Mardanova (483-485).
A series of 4-aroyl-1H-benzo[c]oxepin-4-ones have been prepared by heating ethyl 2-aroyl-3-(2-bromophenyl)propenoates. The synthesized compounds possess higher analgesic activity than the reference drug (analgin) and exhibit low toxicity.
Keywords: analgesic activity; benzooxepinones

Synthesis and antifungal activity of N-aryl-substituted pimaricin derivatives by V. V. Belakhov; Yu. D. Shenin; B. I. Ionin (486-492).
Reactions of the tetraene macrolide antibiotic pimaricin with 1-fluorobenzenes resulted in the formation of N-aryl-substituted derivatives. The physicochemical and biological properties of the synthesized pimaricin derivatives were studied. The N-aryl-substituted pimaricin derivatives showed high antifungal activity against a broad spectrum of test cultures. The biological studies showed that the acute toxicity (LD50) of the obtained pimaricin derivatives was half that of the starting antibiotic.
Keywords: polyene macrolide antibiotics; pimaricin; N-acyl-substituted derivatives; antifungal activity

Synthesis and antifungal activity of 3-aryl-4,4(5H )-dicarbonitrile-5-phenylisoxazolines by S. B. Nosachev; O. V. Degtyarev; V. V. Zhizhikina; A. G. Tyrkov (493-494).
A series of 3-aryl-4,4(5H)-dicarbonitrile-5-phenyloxazolines have been synthesized and tested for activity against Candida albicans, Microsporum canis, and Trichophyton rubrum fungal species.
Keywords: synthesis; 3-aryl-4,4(5H)-dicarbonitrile-5-phenyloxazolines; antifungal activity

Tetracyclic triterpenes from Inonotus Obliquus (Pers.) Pil. (Chaga) growing in Russia by E. N. Zhukovich; M. Yu. Semenova; L. A. Sharikova; T. F. Pribytkova (495-496).
The tetracyclic triterpene content of Inonotus obliquus (Chaga) growing in Russia was investigated for the first time. Lanosterol, inotodiol, and ergosterol were isolated from the non-phenolic fraction. In addition, trametenolic acid was isolated from fraction III, which was prepared by extraction from diethylether solution with 5% NaOH.
Keywords: Chaga; non-phenolic fraction; identification; tetracyclic triterpenoids; lanosterol

Phenolic compounds from two Melampyrum species by E. E. Galishevskaya; V. M. Petrichenko (497-500).
Flavonoids and phenolic acids isolated from the herbs of Melampyrum pretense (MP) and M. nemorosum (MN) (Scrophulariaceae) growing in the Ural region have been studied by two-dimensional paper chromatography. The phenolic complex of MP contains 23 compounds including 17 flavonoids and 6 phenolcarboxylic acids. The MN herb contains 9 flavonoids and 5 phenolcarboxylic acids. A comparison with reference samples showed the presence of cinaroside, luteolin, quercetin, hyperoside, and chlorogenic, caffeic, and ferulic acids. Differential UV spectra of the extracts of MP and MN herbs in the presence of aluminum chloride showed peaks at 395.6 and 398.7 nm, respectively, which have been used for quantitative determination of the flavonoids (recalculated for cinaroside). The maximum flavonoid content was found in the generative organs; the minimum, in the roots. It is established that the flavonoid content in various organs varies within 0.08–3.17% for MP and 0.04–2.29% for MN.
Keywords: Melampyrum pretense ; M. nemorosum ; flavonoids; cinaroside

Biopharmaceutical study of nanosystems containing betulin for inhalation administration by M. V. Karlina; O. N. Pozharitskaya; A. N. Shikov; V. G. Makarov; S. Mirza; I. Miroshnyk; R. Hiltunen (501-503).
Betulin, a triterpenoid present in birch bark, possesses a broad spectrum of biological activity. Its bioavailability is limited by low solubility in water whereas the shape and size of particles are not suited for administration via inhalation. One of the main drawbacks of inhalation preparations is low bioavailability because of the sedimentation of particles in the mouth. The present work was aimed at a biopharmaceutical study of nanosystems with betulin for administration via inhalation. Nanosystems were characterized by photon-correlation spectroscopy, differential scanning calorimetry, and x-ray powder diffraction. In addition, their dissolution profile was obtained by the Dissolution test. It is established that the obtained nanosystems with betulin exhibit high bioavailability, have optimal physicochemical properties for inhalation administration, and ensure deposition of betulin in the lower part of the respiratory tract.
Keywords: betulin; photon-correlation spectroscopy; differential scanning calorimetry; x-ray powder diffraction

Radiopharmaceuticals for radionuclidic diagnostics of bone pathology (review) by T. V. Nalapko; V. G. Skvortsov; Yu. Ya. Kharitonov; N. B. Epstein (504-506).
This review gives a brief outline of the history of development of radiopharmaceuticals (RPh) for radionuclide diagnostics of bone pathology. The advantages of RPh based on 99mTc-diphosphonates are demonstrated.
Keywords: radiopharmaceuticals; bone pathology; radionuclide diagnostics

Hemolytic properties of miltefosine in liposomes of various lipid compositions by M. V. Zhukova; O. V. Romanenko; V. A. Nikolaevich; M. A. Kisel’ (507-509).
The hemolytic activity of hexadecylphosphocholine (HePC) included in liposomes of phosphatidylcholine (PC), phosphatidylethanol (PET), and their mixture in various ratios has been studied. Spectroscopic data suggest that supramolecular particles containing less than 15% HePC occur as liposomes. Hemolysis at the same HePC concentration is less pronounced for liposomes (10% HePC) than for micelles (30% HePC). The inclusion of anionic phosphatidylethanol into the liposomal composition does not affect significantly the degree of hemolysis.
Keywords: miltefosine; hemolytic properties; liposomes

Examination of the structure of agaricinic acid using 1H and 13C NMR spectroscopy by A. Yu. Airapetova; M. V. Gavrilin; A. B. Dmitriev; T. D. Mezenova (510-513).
Agaricinic acid was extracted from the carpophore of Fomitopsis officinalis (Vill. Bond. et Sing). Its structure was established by 1H and 13C NMR spectroscopy and comparison to a standard sample (Sigma—Aldrich). The extraction was carried out using ethanol. The obtained extract was evaporated, cooled (−5°C), and purified by ether. The structure of unbranched alkyl radicals was determined using their proton spectrum. The 13C NMR spectrum and two-dimensional {13C,1H} correlation diagram showed the presence of a hydroxyl (second quaternary C atom) and three types of carboxy groups (first, second, and third C atoms). The spectrum of the extracted sample is identical to that of the standard sample of agaricinic acid.
Keywords: agaricinic acid; Fomitopsis officinalis ; extraction; structure; NMR spectrum

Preparation conditions for samples of biological fluids (urine, blood) for electrophoretic identification of basic nitrogen-containing compounds with the aid of a Kapel-105 capillary electrophoresis system have been studied. It is demonstrated that bupivacaine, lidocaine, and azaleptine can be identified in biological fluids in the presence of coextracted substances using electrophoretic spectra and quantitative indices (pKa).
Keywords: capillary electrophoresis; bupivacaine; lidocaine; azaleptine; coextracted substances of urine and blood; identification by electrophoresis spectrum

Pharmaceutical analysis and standardization of afobazole in solid dosage form (tablets) by L. N. Grushevskaya; S. E. Milkina; O. B. Stepanenko; M. Yu. Volkova; B. M. Pyatin; N. I. Avdyunina; K. V. Alekseev; S. A. Sizyakov (517-520).
The investigation was aimed at developing procedures for the pharmaceutical analysis and standardization of the new domestic anxiolytic afobazole in solid dosage form (tablets). The main pharmacopoeial tests have been carried out and methods for the determination (TLC, HPLC), identification (TLC, UV spectrophotometry), and quantitative assay (UV spectrophotometry, HPLC) have been worked out. The test for uniformity of composition and the dissolution test were carried out with the aid of UVspectrophotometry.
Keywords: afobazole; tablets; pharmaceutical analysis

Sorbents for thin-layer chromatography in pharmaceutical analysis by O. A. Goroshko; O. A. Checha; V. P. Pakhomov; Yu. V. Ruvinov; T. D. Ismagilov (521-524).
Compounds contained in medicinal plant raw material and DL-tryptophan have been separated by thin-layer chromatography using various sorbents including cellulose, RP-modified silica gel, chiral precoated plates, and plates with a concentrating zone.
Keywords: thin-layer chromatography; sorbents; drugs