Pharmaceutical Chemistry Journal (v.42, #12)

Indirect determination of the microsomal oxidase activity of hepatocytes and the effect of ximedone on this activity during streptococcal angina by S. Yu. Garmonov; I. E. Kravchenko; N. S. Shitova; A. V. Yakovleva; R. G. Zaripova; V. Kh. Fazylov (659-664).
The parameters of antipyrine pharmacokinetics in saliva have been calculated and a method for indirect determination of the microsomal oxidase activity of hepatocytes has been developed based on evaluation of the average content of the test compound in sequential 3-h samples of saliva taken over a 12-h period of time after administration. Microsomal oxidase activity has been estimated in patients wth streptococcal angina. It is established that ximedone effectvely influences this activity and produces a positive therapeutic effect on the course of the disorder.

Synthesis and antiarrhythmic activity of quaternary derivatives and mineral salts of diethylaminoacetic acid ortho-toluidide by O. V. Gashkova; V. I. Pantsurkin; I. P. Rudakova; B. J. Syropyatov; M. I. Vahrin (665-667).
A series of quaternary dervatives of diethylaminoacetic acid ortho-toluidide have been synthesized by reactions with various halogen-containing derivatives of alkanes, alkenes, and arylalkanes in acetone. The acute toxicity and antiarrhythmic activity of the synthesized compounds have been studied. Several compounds with antiarrhythmic activity exceeding that of a structural analog (lidocaine) are found and recommended for further investigation and practical implementation.

Synthesis and coronary vasodilating activity of 1-aminopyrazolo[3,4-b]pyridines with fused tetrahydropyran (-thiopyran) and piperidine rings by V. V. Dabaeva; S. G. Pilosyan; A. S. Noravyan; M. P. Bagdasaryan; G. Kh. Grigoryan; R. A. Aleksanyan (668-669).
Methods for the synthesis of 6,6-substituted 1-aminopyrazolo[3,4-b]pyridines with fused tetrahydropyran (-thiopyran) and pyridine rings have been developed on the basis of condensed 2-chloropyridine derivatives. The coronary vasodilating activity of the synthesized compounds has been studied.

Anticancer activity tests have been carried out at the National Cancer Institute (USA) on a series of polycyano-substituted carbo- and heterocyclic compounds synthesized from 3-(2,2-dialkylhydrazino)-4-R-1,1,2,2-tetracyanocyclopentanes. It is established that 1,1,2,2-tetracyano-substituted derivatives are the most active, showing a high activity comparable with that of reference drugs with respect to colon, ovarian, prostate, and renal cancer. The antitumor effect of the investigated compounds is explained by the presence of dialkylhydrazino- and 1,1,2,2-tetracyanoethyl moieties in their structures.

Synthesis and anti-inflammatory activity of 3,1-benzoxazin-4(3H)-ones and N-acyl-5-iodoanthranilic acid amides by E. R. Kurbatov; A. V. Kurochkin; L. M. Korkodinova; B. Ya. Syropyatov; L. N. Markova (674-676).
A series of new 3,1-benzoxazin-4(3H)-ones were synthesized and N-acyl-5-iodoanthranilic acid amides derived from them were obtained in a search for new biologically active derivatives of anthranilic acid. The anti-inflammatory activity of these compounds was evaluated. It is established that these classes of compounds are promising for further research on biologically active substances possessing anti-inflammatory activity.

Novel approaches on prodrug based drug design by A. Rasheed; C. K. A. Kumar (677-686).
Prodrug design is really not different from the general drug discovery process, in which a unique substance is observed to have desirable pharmacological effects, and studies of its properties lead to the design of better drugs. It is a very fruitful way of research, and its introduction in human therapy has given successful results in improving the clinical and therapeutic effectiveness of drugs suffering from some undesirable properties that otherwise hinder their clinical usefulness. The present article reviews various prodrugs and their applications and presents the developments in this field during the last few decades. This review also highlights developing strategies in targeted prodrug design, including antibody-directed enzyme prodrug therapy, gene-directed enzyme prodrug therapy and peptide transporter-associated prodrug therapy.

Synthesis, characterization, and thermal and biocidal aspects of drug-based metal complexes by M. N. Patel; P. B. Pansuriya; P. A. Parmar; D. S. Gandhi (687-692).
Drug-based metal complexes [M(L)(A)(H2O)2] (M = Cu(II), Ni(II), Co(II), Zn(II), Cd(II), Mn(II), A = atenolol and L = ciprofloxacin) have been prepared and characterized using infrared spectra, electronic spectra, magnetic measurements, elemental analyses, and thermal investigation. Spectral investigations of metal complexes assume monomeric six-coordinate octahedral geometry. All the synthesized complexes exhibit higher biocidal activity against Bacillus subtilis, Escherichia coli, Bacillus cereus, Staphylococcus aureus, Salmonella typhi, and Serratia marcescens compared to parent compounds and standard drugs.

Role of P-glycoproteins in the transepithelial transport of indoline alkaloids isolated from Vinca herbaceae by L. K. Tsiklauri; H. Hoyer; G. V. Chkhikvadze; V. Yu. Vachnadze; G. V. Tsagareishvili; A. G. Bakuridze; A. Bernkop-Schnurch (693-695).
The permeability of anti-arrhythmic crude alkaloids (Vingerbine preparation) from Vinca herbaceae W. et Kit. across rat intestine has been demonstrated for the first time. The results suggest that P-glycoproteins (P-gps) are involved in the preferential transport of vincarine and herbadine, compounds bearing a hydrogen atom on a secondary N (N―H), in the basolateral to apical direction. However, P-gp/MDR1 play a minor role in the intestinal transport of herbamine and vincamajine, compounds with substituted N (N―CH3). In order to improve peroral bioavailability and achieve maximum therapeutic efficiency of Vingerbine, further research will be focused on finding a strategy to overcome the P-gp barrier and developing suitable delivery systems.

A phytochemical study of the fruits of Elaeagnus angustifolia L. occurring in the Central Nonchernozem region of the Russian Federation has been performed. Qualitative reactions and quantitative instrumental methods of analysis proved the presence of polysaccharides, flavonoids, coumarins, phenolcarboxylic acids, amino acids, saponins, carotenoids, vitamins, and tannins. The quantitative content of the biologically active compounds has been estimated. It is shown that the fruits of Elaeagnus angustifolia occurring in Russia are a promising source of compounds presenting considerable interest for the pharmacy and food industry.

The composition of lipophilic fractions of homeopathic matrix tinctures of Urtica dioica L. (I) and U. urens L. (II) derived from freshly collected plants and dried (desiccated) material (herb and roots) was studid using GC-MS techniques. The analyses of n-hexane extracts of tincture I revealed 43 compounds (of which 27 were identified) whereas the analysis of the extract of tincture II revealed 28 compounds (21 identified). The extract from I contains fatty acids in the form of ethyl esters, terpenoids (apiol, eugenol), squalene, and some other substances. The main fatty acids are palmitic, linolenic, and nonadecanoic. Tincture of I obtained from a desiccated raw material contains ethyl esters of linoleic and 2,3-benzofurandicarboxylic acids, which are not found in II. Tincture obtained from freshly collected material contains greater amounts of ethyl esters of oleic, 9-oxononanoic, 4-hydroxy-3-methoxybenzoic acids, 3-ethyl-4-methyl-(1H)-pyrrol-2,5-dione, 5,6,7,7a-tetrahydro-2(4H)-benzofuranone, and eugenol. The extract of tincture II contains significant amounts of palmitic, linoleic, and linolenic acids and 3,7,11,15-tetramethyl-2-hexadecen-1-ol. Some of the identified substances, including ethyl esters of heptadecenoic, arachic, 8,11-eicosadienoic, heneicosanoic, and behenic acids were detected only in the tincture from dried (desiccated) raw material. The lipophilic fraction of matrix tinctures from U. dioica root contain large amounts of linoleic, linolenic, and nonadecanoic acids and their isomers in addition to palmitic, myristic, 9-oxononanoic, and pentadecanoic acids. The content of identified components was greater in the tinctures from freshly collected material (except for squalene, the concentration of which increases by a factor of about four in the tincture prepared from desiccated material).

Technology and analysis of temperature-sensitive liposomal preparation of doxorubicin by E. V. Tazina; E. V. Ignat’eva; A. P. Polozkova; O. L. Orlova; N. A. Oborotova (703-707).
The optimum composition of temperature-sensitive liposomes (TSLs) has been chosen and a method of doxorubicin loading in TSLs by ammonium ion gradient has been developed. The TSL-encapsulated doxorubicin was lyophilized for better stabilization with 4.0% sucrose added as a cryoprotective agent. A method based on spectrophotometry at 252 nm is proposed for the determination of oxorubicin concentration in TSLs. It is established that TSLs encapsulate 89.5 ± 3.5% of doxorubicin. The particle size of the vesicles is 165 ± 10 nm. The proposed TSL doxorubicin formulation possesses selective action, shows higher efficiency and lower toxicity in comparison to the traditional doxorubicin, and can be recommended for use in the chemo-thermotherapy of solid tumors.

Synthesis and characterization of coordination compounds of silver and tryptophan by G. M. Bobiev; T. Sufiev; A. N. Shakhmatov; Kh. Sh. Abdulov (708-711).
It is shown using the isomolar series method that the synthesis of coordination compounds of silver and tryptophan both by direct interaction of AgNO3 with tryptophan and via the formation of an intermediate silver hydroxide yields target compounds with silver:tryptophan molar ratios 1:2, 1:1, and 2:1. It is established by pH-titration that synthesis of coordination compounds of silver and tryptophan via the intermediate silver oxide forms four complexes with logarithms of stability constants log $$log {upbeta} _{{{left[ {{ ext{Ag}}{left( {{ ext{HL}}^{ pm } } ight)}} ight]}^{ + } }} = pm 5.824$$ , $$log {upbeta} _{{{left[ {{ ext{Ag}}{left( {{ ext{HL}}^{ pm } } ight)}^{2} } ight]}^{ + } }} = - 3.523$$ , $$log {upbeta} _{{{left[ {{ ext{AgL}}} ight]}^{0} }} = 4.103$$ , $$log {upbeta} _{{{left[ {{ ext{AgL}}_{{ ext{2}}} } ight]}^{ - } }} = 6.805$$ , and $$log {upbeta} _{{{left[ {{ ext{AgL}}{left( {{ ext{HL}}} ight)}} ight]}}} = 5.771$$ .

IR spectroscopy has been used for the first comparative study of the kinetics of reaction of dopamine with acetaldehyde in the presence and absence of unithiol (sodium salt of 2,3-dimercapto-1-propanesulfonic acid, DMPS), a vicinal dithioglycol. Based on the analysis of these reactions, it is concluded that the rate of interaction between acetaldehyde and dopamine decreases significantly in the presence of unithiol, which is a new kind of pharmacological activity for unithiol. This property of unithiol allows it to be recommended for further investigation aimed at the development of a new remedy capable of inhibiting the development of alcohol addiction.

Phase equilibria in dispersed solid systems of ibuprofen with piracetam and urea as hydrophilic components by L. E. Zhnyakina; M. L. Tkachenko; Yu. V. Moshchenskii; I. P. Ivanova (716-718).
The solid dispersion systems ibuprofen-piracetam and ibuprofen-urea have been studied by differential scanning calorimetry. It is established that these systems belong to the eutectic type. The points of nonvariant equilibrium of the ibuprofen-piracetam and ibuprofen-urea systems correspond to a 65:35 and 74:26 (mol%) ratio of components, respectively. The solubility of ibuprofen from the solid binary mixtures increases with increasing fraction of very soluble components. For the ibuprofen-piracetam and ibuprofen-urea eutectic systems, the solubility of ibuprofen increases by a factor of approximately 2 and 1.53, respectively, as compared to the pure substance alone.

Fast and easy GC/MS identification of myrrh resins by L. O. Hanuš; D. Rosenthal; T. Řezanka; V. M. Dembitsky; A. Moussaief (719-720).
Extracts prepared from Commiphora molmol resins were analyzed by GC-MS. Twenty-two terpenoid compounds were identified in the hexane extract of the resin. Among them, 2-acetoxyfuranodiene (9.80%), furanoeudesma-1,3-diene (8.97%), isofuranogermacrene (6.71%), epicurzerenone (3.64%), 2-methoxyfuranodiene (2.97%), and lindestrene (2.74%) were the main compounds from the first myrrh resin (Tamar Ltd.), and furanoeudesma-1,3-diene (20.59%), isofuranogermacrene (17.94%), 2-acetoxyfuranodiene (8.80%), 2-methoxyfuranodiene (7.33%), and lindestrene (6.24%) from the second myrrh resin (Pamir Ltd.).

Evaluation of the purity of vitamin a oil-based preparations by thin-layer chromatography by O. V. Checheta; E. F. Safonova; A. I. Slivkin; G. A. Ogol’ (721-723).
An important stage in pharmaceutical analysis is the estimation of the degree of purity of parent substances and related preparations. There is currently a need to develop simple, economic, and accessible methods for rapid analysis. One such method is thin-layer chromatography (TLC). In the present work, the possibility of using TLC for monitoring the content of impurities in oil-based vitamin A preparations and for their separation and identification is considered.

Validating the analytical method for the reference sample of lappaconitine by I. M. Faizrakhmanova; E. M. Tsirlina; M. S. Yunusov; Yu. I. Murinov; G. I. Minazova (724-725).
A method for the quantitative determinnation of the reference sample of lappaconitine by HPLC has been developed and included in the draft of the pharmacopoeic article for this drug. The proposed analytical technique is completely validated and includes the entire complex of characteristics for the specificity, suitability of the chromatographic system, and the linearity, accuracy, and reproducibility of the HPLC analyses.

Comparative in vitro dissolution testing of indapamide prolonged-release tablets by G. V. Ramenskaya; V. S. Shlykov; O. A. Dekhanova (726-729).
The results of dissolution testing of five modified release dosage forms of indapamide are presented. It is shown that comparative analysis of dissolution profiles can be used to develop in vivoin vitro correlations and to establish the similarity of drug bioavailability in various ready-to-use dosage forms for which the composition, technology, or scale of manufacturing may have been changed.