Pharmaceutical Chemistry Journal (v.42, #9)

Influence of amitriptyline, chlorpromazine, and imipramine on the activity of phosphohydrolases by L. V. Tat’yanenko; O. V. Dobrokhotova; D. V. Mishchenko; G. N. Bogdanov; Ya. R. Nartsissov (497-500).
We have studied the effects of the antidepressants amitriptyline and imipramine and the neuroleptic chlorpromazine on the enzymatic function of Ca2+-activating-Mg2+-dependent ATPase of sarcoplasmic reticulum (SR), Na+, K+-dependent ATPase of endoplasmic reticulum (ER), and phosphodiesterase of cyclic adenosine monophosphate (cAMP). It is shown that interference with the enzymatic function (decrease of [Ca2+]/[ATP]) or inhibition of active transport of calcium ions by Ca2+, Mg2+-ATPase of SR by the psychotropic drugs leads to impairment of Ca2+ transport into the SR vesicule, which increases the force of muscle contraction. This effect decreases with increasing concentrations of amitriptyline and imipramine and with decreasing concentration of chlorpromazine, which is evidence for different mechanisms of action of Ca2+, Mg2+-ATPase of SR. Amitriptyline was a noncompetitive reversible inhibitor of Ca2+, Mg2+-ATPase of SR with an ATP hydrolysis inhibition constant Ki = 1.8 × 10−4 M and an active calcium transport inhibition constant Ki = 0.7 × 10−4 M. The goal of the investigation was to study the molecular mechanisms of action of amitriptyline, imipramine, and chlorpromazine.

Modulation of contractile enzyme activity by anticonvulsant drugs by L. V. Tat’yanenko; O. V. Dobrokhotova; D. V. Mishchenko; G. N. Bogdanov; Ya. R. Nartsissov (501-503).
Anticonvulsant drugs of the heterocyclic amide family inhibit in vitro enzymatic activity of Ca2+, Mg2+-ATPase of sarcoplasmic reticulum, the activated transmembrane calcium-ion transfer/ATP hydrolysis specific rate ratio being retained to provide lower concentrations of calcium ions in myofibrilla and relaxed muscles. Ethosuximide is a noncompetitive inhibitor with reversible action on basic enzyme catalyzed processes. The inhibition of the hydrolytic activity of the enzyme under the action of ethosuximide, phenytoin, and primidone was compared to their effect on other phosphatases (cAMP phosphodiesterase and Na+, K+-dependent ATPase).

Antitumor activity of substituted methylglyoxal bisthiosemicarbazones and their copper(II) chelates by E. R. Dilanyan; T. R. Ovsepyan; F. G. Arsenyan; G. M. Stepanyan; B. T. Garibdzhanyan (504-506).
A series of new bisthiosemicarbazones of methylglyoxal and their copper(II) complexes were synthesized. Evidence of antitumor properties of some products combined with low toxicity shows that further searching for antitumor agents in this group of compounds may be promising.

Synthesis and biological activity of 3-methyl-3-(3′-aminothiazol-4-yl)-8-alkoxymethyl-2,7-dioxaspiro[4,4]nonane-1,6-diones by T. V. Kochikyan; M. A. Samvelyan; V. S. Arutyunyan; A. A. Avetisyan; R. V. Paronikyan; G. M. Stepanyan (507-509).
A method for obtaining derivatives of γ-dilactones, 3-methyl-3-(3′-amino[or substituted amino]thiazol-4-yl)-8-alkoxymethyl-2,7-dioxaspiro[4, 4]nonane-1,6-diones, has been developed. Their antibacterial and antitumor properties have been evaluated. Compounds possessing low toxicity and weak antitumor activity have been found in the series of γ-dilactone derivatives.

Synthesis and rheological activity of new 1,2,4-triazole derivatives by E. E. Klen; F. A. Khaliullin; A. A. Spasov; N. N. Makarova; L. F. Bagautdinova; L. V. Naumenko (510-512).
Reactions of 3,5-dibromo-1,2,4-triazoles containing thietane or thietane-1,1-dioxide with thioglycolic acid yielded 2-[1-(thietanyl-3)-or 2-[1-(1,1-dioxothietanyl-3)-3-bromo-1,2,4-triazolyl-5-thio]acetic acids. Their salts have also been synthesized via reactions with amines and alkalis. Evaluation of the rheological properties showed that some of the synthesized compounds exhibited antiaggregant activity with respect to erythrocytes that was comparable with the effect of pentoxifylline.

A series of 1,6-disubstituted 2,5-dibromohexan-1,3,4,6-tetraones and 2,2,5,5-tetrahalogenohexan-1,3,4,6-tetraones have been obtained by the treatment of 1,6-disubstituted hexane-1,3,4,6-tetraones with bromine and chlorine. Bromination of (4Z)-6-aryl-3,4-dihydroxy-6-oxohexa-2,4-dienamides led to (2Z,4E)-2-aminocarbonyl-6-aryl-5-bromo-3,4-dihydroxy-6-oxohexa-2,4-dienoates and 6-aryl-2,5-dibromo-3,4,6-trioxohexanamides in preparative yield. The proposed structures of the reaction products were confirmed by IR, UV, 1H and 13C NMR, and mass spectrometry. The bacteriostatic activity and acute toxicity of the synthesized compounds have been studied.

Synthesis and antimicrobial properties of 2-chloro(bromo, thiocyanato)-1-aryl-2-methyl-3-chloropropanes by P. M. Gorbovoi; F. N. Tulaidan; B. D. Grishchuk; S. I. Klimnyuk; E. V. Pokryshko (520-522).
A series of 2-chloro(bromo, thiocyanato)-1-aryl-2-methyl-3-chloropropanes have been synthesized. Their antimicrobial properties have been evaluated. The most effective compounds were 2-chloro-1-phenyl-2-methyl-3-chloropropane and 2-bromo-1-p-methylphenyl-(1-p-methoxyphenyl)-2-methyl-3-chloropropane.

A series of new mixed-ligand coordination complexes of copper with sulfazine and benzoylhydrazones of salicylaldehyde and 5-chloro-, 5-bromo-, 5-nitro-, 3,5-dichloro-, and 3,5-dibromosalicylaldehydes have been synthesized. The compounds display high antimicrobial activity. The compositions and probable structures of the obtained complexes have been proposed on the basis of elemental analysis, magnetic measurements, IR spectroscopy, and thermogravimetric measurements. The influence of the anion and the substituent in the salicylaldehydebenzoylhydrazone fragment on the structure and antimicrobial activity of coordination compounds toward nine Gram-positive and Gram-negative microorganisms has been studied. Sulfazine-containing copper(II) chloride and bromide complexes obtained on the basis of 3,5-dibromosalicylaldehydebenzoylhydrazone showed the maximum antimicrobial activity.

Synthesis and antimicrobial activity of β-N-acylhydrazides of 4-aryl-2-hydroxy-4-oxo-2-butenoic (aroylpyruvic) acids by O. V. Zvereva; A. V. Milyutin; T. F. Odegova; E. N. Fedorenko (527-528).
A series of β-N-acylhydrazides of 4-aryl-2-hydroxy-4-oxo-2-butenoic (aroylpyruvic) acids have been synthesized in 80–90% yield via decyclization reactions of 5-aryl-2,3-dihydrofuran-2,3-diones with hydrazides of aromatic acids in anhydrous dioxane. Physicochemical characteristics of the products were determined. Their antimicrobial properties were examined.

Reaction of substituted o-aminophenols with acylpyruvic acid esters and α-ketoglutaric acid. Antibacterial activity of the products by V. L. Gein; N. A. Rassudikhina; N. V. Shepelina; M. I. Vakhrin; E. B. Babushkina; E. V. Voronina (529-532).
Reaction of methyl esters of acylpyruvic acids with substituted o-aminophenols led to 6(7)-substituted 3-acylmethylene-1,4-benzoxazin-2-ones. Reaction of substituted o-aminophenols with α-ketoglutaric acid led to 6-substituted 3-carbonyl-1,4-benzoxazin-2-ones. The structures of the synthesized compounds were confirmed by IR and NMR spectroscopy and mass spectrometry. The antibacterial activity of the compounds was studied.

Synthesis and antibacterial activity of 3,4-dihyhdropyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-ones by E. S. Kostenko; E. A. Kaigorodova; I. V. Serdyuchenko; V. I. Terekhov; L. D. Konyushkin (533-535).
A series of 3,4-dihydropyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-ones were synthesized by the reaction of ethyl 3-alkyl(aryl)carboxamidothieno[2,3-b]pyridine-2-carboxylates with aliphatic amines. The starting carboxamides were obtained via the reaction of ethyl 3-aminothieno[2,3-b]pyridine-2-carboxylate with acid chlorides. It is established that the synthesized pyridothienopyrimidinones possess antistaphylococcal activity.

New syrup compositions Flavozid and Immunoflazid that contain 2% Proteflazid (ethanol extract of wild Deschampsia caespitosa L. and Calamagrostis epigeios L.) have been developed. The total content of flavonoids in both syrups is of the level of 4–6 µg/mL, which complicates the development of an analytical method. A new method for quantitative determination of flavonoids in the aforementioned syrups has been developed on the basis of differential UV spectrophotometry of their complexes with aluminum chloride. The proposed method is introduced into the Manufacturer's Pharmacopoeic Article for the syrups.

High-performance liquid chromatography with UV and amperometric detection has been used to analyze qualitatively and quantitatively phenolic extracts of several plants used in the production of drugs, food, and cosmetics. Phenolic compounds in aqueous alcohol, alcohol, and propyleneglycol (PPG) extracts were identified as groups using a previously constructed database of the spectra and retention times of 74 phenolic compounds. The antioxidant activity (AA) of the extracts was measured as the sum of peaks on the chromatograms after the amperometric detector. The AA of the alcohol extracts correlated with the flavonoid content. Extracts obtained using supercritical PPG had the maximum AA.

It is established that mixed-valence ruthenium oxide-ruthenium cyanide deposited on a glassy carbon electrode surface possesses catalytic activity for oxidation of tetracycline antibiotics (tetracycline, oxytetracycline, doxycycline). The catalytic effect consists of a decrease in the potential of tetracycline oxidation by about 200 mV and in a multiple increase of the oxidation current. A method is proposed for determining tetracycline, oxytetracycline, and doxycycline using the electrocatalytic response of a chemically modified electrode with a RuO-RuCN film under batch and flow-injection analysis conditions. The catalytic current depends linearly on the concentration of tetracycline antibiotics from 5 mM to 0.5 µM and 50 nM under batch and flow-injection analysis conditions, respectively.

Harmonization of quality indicators of the domestic parent substance fentanyl by U. A. Murashova; L. V. Skalkina; N. P. Sadchikova; S. K. Smirnov (550-552).
We present a comparative analysis of the methods for quality evaluation and standardization of the parent substance of fentanyl based on foreign pharmacopoeias and domestic regulations. Harmonization of the tests and norms is proposed for the sections identification, determination of foreign impurities, and quantification. The harmonization is carried out at the stage of monograph preparation for the revised version of existing regulations.