Pharmaceutical Chemistry Journal (v.42, #6)

Antianemic activity of polymetallocomplexes of pectin polysaccharides with Fe2+, Co2+, and Cu2+ with different ratios of d metals by A. B. Vyshtakalyuk; A. N. Karaseva; V. V. Karlin; S. T. Minzanova; V. F. Mironov; A. I. Konovalov (309-312).
The antianemic activity of water-soluble polymetallocomplexes of pectin polysaccharides containing d metal ions — Fe2+, Co2+, and Cu2+ — at different ratios was studied in laboratory rats. The results showed that complexes had marked stimulatory effects on hematopoietic processes, with increases in hemoglobin concentrations and erythrocyte counts, along with intensification of the recovery of hematological parameters after anemia induced by hemorrhage. The highest level of activity on hematological measures was obtained with the polymetallocomplex containing Fe2+, Co2+, and Cu2+ ions at a ratio close to 1:1:1.

Synthesis and biological properties of 3-phenyl-and 3-phenethyl-5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines by A. I. Markosyan; Kh. S. Akalyan; F. G. Arsenyan; R. S. Sukasyan; B. T. Garibdzhanyan (313-318).
The interaction of 3-methyl-3-ethyl-1-amino-2-ethoxycarbonyl-3,4-dihydronaphthaline with phenyl-and phenethylisothiocyanates and subsequent treatment of the reaction mix with alkali led to the formation of the corresponding 3-phenyl-and 3-phenethyl-5-methyl-5-ethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazolines (II, III). Condensation of the resulting 2-thioxobenzo[h]quinazolines II and III with halogenides of different structures was used to synthesize 2-sulfanyl-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (IV–XXVII). Reaction of benzo[h]quinazoline II with 2-ethanolamine and 3-propanolamine yielded 5-methyl-5-ethyl-3-phenyl-2-(β-hydroxyethylamino)-and 5-methyl-5-ethyl-3-phenyl-2-(γ-hydroxypropylamino)-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (XXVIII, XXIX) respectively. The effects of the resulting compounds on brain monoamine oxidase (MAO) activity were studied in in vitro experiments. Most of the compounds were found to inhibit 5-HT deamination. The antitumor activities of these compounds were studied using two models of grafted mouse tumors — Ehrlich ascites carcinoma (EAC) and sarcoma 180. Some of the study compounds had moderate therapeutic effects (suppressing tumor growth by 50–60%, p < 0.05).

Synthesis and anti-inflammatory activity of acyl derivatives of taraxasterol by É. R. Shakurova; T. I. Parfenova; R. Sh. Sufiyarova; A. Z. Khalilova; V. R. Akhmetova; S. A. Bashkatov (319-321).
Acylation of taraxasterol with acid chloranhydrides in the presence of N-dimethylaminopyridine yielded the new compounds 3β-acetoxy-20-methylidenetaraxastane, 3β-trifluoroacetoxy-20-methylidenetaraxastane, and 3β-benzoyl-20-methylidenetaraxastane. The antiphlogistic activities of taraxasterol and its acyl derivatives were studied. All study compounds had anti-inflammatory activity comparable to that of reference agent prednisolone.

Reactions of the polyene macrolide antibiotic nystatin with trialkylchlorosilanes led to the formation of N-alkylsilyl derivatives. The physicochemical and biological properties of the resulting nystatin derivatives were studied. Organic silicon derivatives of nystatin had high levels of antifungal activity against a wide set of test strains. Biological studies showed that the acute toxicity (LD50) of the resulting nystatin derivatives were 2–3 times lower than that of the initial antibiotic.

Synthesis and antimicrobial activity of sulfanilamide-containing copper (II) naphthalidenethiosemicarbazidates by A. P. Gulya; V. I. Prisakar; V. I. Tsapkov; S. A. Buracheva; S. N. Spynu; N. P. Bezhenar (326-328).
Aseries of copper (II) streptocide-, sulfacyl-, norsulfazole-, ethazole-, and sulfadimezine-containing naphthalidenethiosemicarbazidates and napthalidene-4-phenylthiosemicarbazidates with high levels of antimicrobial activity were synthesized. Elemental analysis, magnetochemical, IR spectroscopic, and thermogravimetric data were used to confirm the compositions and structures of the resulting complexes. The effects of the nature of the central atom and the influences of the sulfanilamide and phenyl radicals in the azomethine thiosemicarbazone fragment on the antimicrobial activity of the compounds against 10 strains of Gram positive and Gram negative microorganisms were studied. The most active of the compounds synthesized were the copper norsulfazole-, ethazole-, and sulfadimezine-containing naphthalidenethiosemicarbazidates.

Classificatory and quantitative models of the relationship between the structures of chemical compounds and their toxicity for Daphnia magna by O. A. Raevskii; A. N. Razdol’skii; V. D. Tonkopii; I. V. Iofina; A. O. Zagrebin (329-334).
A structural similarity method was used to construct stable classificatory models for discriminating compounds with mechanisms of general toxicity to Daphnia magna compared with all other compounds with different actions, compounds with the polar narcosis mechanism compared with all others, compounds inhibiting cholinesterase compared with compounds with other mechanisms, and compounds with general toxic actions compared with substances with the polar narcosis mechanism. Simultaneous use of the classificatory and regression models allowed clear identification of substances acting via the general toxicity mechanism, with quantitative assessments of LC50 values and analysis of contributions of steric interactions and hydrogen bonds to toxicity. Our own experimental data on the toxicities (LC50) of 119 chemical compounds with different types of toxic actions to Daphnia magna are presented.

Antibacterial, antifungal, antiherbicidal, and antifungicidal activity of 4,6-dimethoxyhomophthalic acid and related compounds by Ghulam Qadeer; Nasim Hasan Rama; Muhammad Zareef; Najim A. Al-Masoudi (335-339).
4,6-Dimethoxyhomophthalic acid (5) has been synthesized efficiently in four steps from 3,5-dimethoxycinnamic acid (1) and characterized and screened for their in vitro antibacterial activity against four Gram negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhii, and Shigella flexneri) and two Gram-positive (Bacillus subtilis and Staphylococcus aureus) bacterial strains, and for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani, and Candida glaberata. The compounds were screened for their in vitro antiherbicidal and antifungicidal activities.

Chemical composition and pharmacological activity of the leaves of Pueraria hirsuta L. grown in Georgia by É. P. Kemertelidze; V. N. Syrov; M. D. Alaniya; N. Sh. Kavtaradze; Z. A. Khushbaktova (340-343).
Phenolic compounds from Pueraria hirsuta L. grown in Georgia were studied. The leaves yielded the flavonoids robinin, nicotiphlorin, rutin, and the isoflavone glycoside daidsin; the roots yielded the isoflavones daidsin, daidsein, phormononetin, ononin, and the coumestan mirificoumestan. The dominant flavonoid in leaves was robinin, with contents of up to 1.7%. Dry extract of Pueraria hirsuta leaves containing the whole complex of biologically active compounds decreased urea, residual nitrogen, and creatinine levels in serum both in intact rats and in rats with acute renal failure induced by mercury dichloride. In terms of its hypoazotemic activity, the extract was as active as the therapeutic agent lespenephril. The functional state of the monooxygenase system of the cytoplasmic reticulum of kidney cells plays the defining role in the mechanism of the hypoazotemic action of the extract.

An Eritrichium sericeum Lehm. (Boraginaceae) cell culture — a source of polyphenol compounds with pharmacological activity by V. M. Bryukhanov; V. P. Bulgakov; Ya. F. Zverev; S. A. Fedoreev; V. V. Lampatov; M. V. Veselova; O. V. Azarova; O. N. Zyablova; Yu. V. Inyushkina (344-347).
Polyphenol compounds consisting of caffeic acid oligomers were detected in cell cultures from Eritrichium sericeum Lehm.: (−)-rabdosiin, (+)-rosmarinic acid, and eritrichin; the quantitative contents of individual polyphenols were determined. The total content of polyphenol compounds in biotechnological raw material was 6.9% of dry tissue weight, which was 26.5 times greater than the content in the roots of the native plant. Studies of the pharmacological activity of the experimental Eritrichium sericeum Lehm. preparation, containing a complex of polyphenol compounds, demonstrated increases in renal excretory function and suppression of the exudative stage of inflammation as a result of prolonged use of the cell culture phytocomplex at a dose of 100 mg/kg.

Experimental studies of the hypolipidemic properties of pollen by Yu. K. Vasilenko; I. V. Dukhanina; G. D. Lazaryan (348-350).
Experiments on white rats with a model of “chronic” (two months) hyperlipidemia demonstrated the ability of pollen to produce significant delays in increases in blood cholesterol, triglycerides, and beta-lipoproteins and in liver cholesterol; pollen increased blood alpha-lipoprotein cholesterol. The effects of pollen approached those of Lipanor. The hypolipidemic action of pollen was linked with a reduction in cholesterol uptake and an increase in its metabolism into bile acids, along with reductions in peroxidation, membrane stabilization, and activation of adaptive anabolic reactions in tissues.

Studies of iridoids from Dracocephalum moldavica cultivated in the Stavropol Region by O. I. Popova; A. S. Nikitina; O. M. Markova (351-353).
The Moldavian dragonhead Dracocephalum moldavica L., of the Lamiaceae family, is a grassy annual plant up to 80 cm tall. The herbaceous part contains an essential oil, flavonoids, iridoids, tannins, and hydroxycinnamic and carboxylic acids. The quantitative composition of the iridoid glycosides was studied using aqueous and alcoholic extraction of Moldavian dragonhead herb. Chromatography was performed on “Sorbfil” plates using a variety of solvent systems. Compounds were identified in terms of the luminescence-chromatographic characteristics of spots on chromatograms and R f values. Extracts were found to contain from four to six iridoid compounds, of which spots with R f values of 0.43 and 0.89 were identified as harpagide and harpagide acetate respectively. The quantitative contents of iridoid glycosides were evaluated by spectrophotometry based on estimation of the products of the hydroxamic reaction. Harpagide acetate was selected as the standard substance. The relative estimation error with confidence limits of 95% was ± 2.8%. The investigations reported here showed that the optimum conditions for estimating iridoid contents were as follows: particle size no greater than 1 mm with extraction of starting material with 70% ethanol at a ratio of 1:40 for 1 h in a boiling water bath. Iridoid contents were determined in Moldavian dragonhead herb prepared at the budding stage (0.11–0.27%), at mass flowering (0.18–0.51%), and at fruiting (0.04–0.30%); the greatest iridoid content (0.51%) in the herbaceous parts of the Dracocephalum moldavica was seen at the mass flowering phase.

Studies of the biological activity of an oil extract of the snakeflower Lamium album by N. M. Petukhova; A. V. Buryakina; E. L. Avenirova; M. A. Burakova; E. V. Drozhzhina (354-356).
An oil extract was prepared from the above-ground part of the snakeflower Lamium album; this contained a total chlorophyll derivative content of 0.46 ± 0.02 mg/ml. The extractant was a biphasic system consisting of ethanol and sunflower oil. Studies of the biological activities of the snakeflower oil extract were performed in models of hemolytic and iron-deficiency anemia. The antianemic activity of Lamium album L. was assessed in each of these models.

Preparation of lidocaine, bipuvacaine, mepivacaine, trimecaine, and pyromecaine by reductive acylation on palladium catalysts by M. G. Abdullaev; M. V. Klyuev; Z. Sh. Abdullaeva; B. K. Kurbanov; A. N. Idrisova (357-359).
A method for the catalytic synthesis of local anesthetics — lidocaine, bipuvacaine, mepivacaine, trimecaine, and pyromecaine — by reductive acylation is described. The process takes place in mild conditions (20–50°C, hydrogen at atmospheric pressure, organic solvent) with target product yields of 54–93%.

Immobilization of Penicillium solitum lipase on the carbon fiber material “Dnepr-MN” by I. I. Romanovskaya; G. I. Bondarenko; T. I. Davidenko (360-362).
A method for immobilizing Penicillium solitum lipase (the medicinal agent Solizyme) on the activated carbon fiber material “Dnepr-MN” is proposed; using a matrix with total pore volumes of 0.41–1.3 cm3/g, the method allows the enzyme:matrix ratio (1:30–1:60) to be controlled, yielding preparations with a specified lipolytic activity (20–40 LU/mg of agent) at quantitative yield (91–97%). Studies of the pH and temperature stability, functioning in acid media, and desorption demonstrated stabilization and prolongation of the lipolytic activity of the immobilized lipase.

Radiation sterilization of medicinal formulations of doxorubicin bound to poly(butylcyanoacrylate) nanoparticles by O. O. Maksimenko; E. P. Pavlov; É. G. Tushov; A. A. Molin; Yu. V. Stukalov; T. N. Prudskova; P. G. Sveshnikov; J. Kreuter; S. É. Gel’perina (363-367).
Polybutylcyanoacrylate nanoparticles represent a potential system for delivering medicinal agents. The present report describes development of a method for radiation sterilization of medicinal formulations of doxorubicin based on polybutylcyanoacrylate nanoparticles. The physicochemical properties of the medicinal formulation were studied after gamma irradiation and irradiation with accelerated electrons over the dose range 10–35 kGy. The chemical structure of doxorubicin and the polymer carrier was found to be intact after irradiation at a dose of 25 kGy. Irradiation at these doses also had no effect on the colloidal properties of polymer nanoparticles, which retained their stability to aggregation and sedimentation. The optimum sterilizing dose was 15 kGy.

Physical-chemical characterization and quality control of spironolactone raw material samples by F. C. Brandão; M. P. Tagiari; M. A. S. Silva; L. F. Berti; H. K. Stulzer (368-376).
It is well established that solid-state properties such as solubility, particle size, and morphology are critical factors in the development of pharmaceutical formulations. Thus, the evaluation of the physical-chemical properties of the substances that will be used must be the primary step for quality control in the pharmacy industry. The aim of this report is to characterize and to establish the quality of four spironolactone raw samples, derived from distinct laboratories, through thermal analysis (DSC and TG), infrared spectroscopy (IV), solubility assay, scanning electron microscopy, and digital image analysis. Capsules of spironolactone were also prepared with these different drug samples and dissolution profiles determined. The IR and the DSC assays confirmed the identity of the samples as spironolactone. Morphological differences relating to shape, size, and particle size distribution were found and can be directly related to the varied dissolution profiles presented by the different formulations.