Pharmaceutical Chemistry Journal (v.47, #6)

Recent advances in the pharmacological treatment of hormonal hyperfunction and insufficiency of adrenal glands were reviewed.
Keywords: adrenals; corticosteroids; inhibitors; Itsenko–shing’s disease; malignant tumors; adrenal gland cortex insufficiency

Effect of an Inclusion Complex of an Aminomethylated Dihydroquercetin Derivative in Cyclodextrin on Ozone-Induced Oxidation of Fibrinogen by V. S. Rogovsky; T. M. Arzamasova; M. A. Rosenfel’d; M. L. Konstantinova; V. B. Leonova; S. D. Razumovskii; A. I. Matyushin; N. L. Shimanovskii; A. M. Koroteev; S. E. Mosyurov; M. P. Koroteev; T. S. Kukhareva; É. E. Nifant’ev (295-298).
The ability of a water-soluble inclusion complex (KN-14-CD) of an aminomethylated dihydroquercetin derivative (KN-14) in β-cyclodextrin (CD) to inhibit ozone-induced oxidation of fibrinogen was evaluated. KN-14-CD prevented ozone-induced oxidation of fibrinogen and preserved its ability to form clots after the addition of thrombin. The ability of KN-14-CD to prevent oxidative modification of fibrinogen was more pronounced than that of native dihydroquercetin (taxifolin).
Keywords: KN-14-CD; taxifolin; cyclodextrin; dihydroquercetin; oxidative damage of fibrinogen; ozone-induced oxidation

Synthesis and Use of Hyaluronic Acid–10B Polymeric Chelates for Neutron-Capture Therapy by S. N. Koryakin; P. L. Ivanov; V. N. Khabarov; V. A. Yadrovskaya; E. V. Isaeva; E. E. Beketov; A. N. Zelenetskii; S. A. Uspenskii; M. A. Selyanin; S. E. Ulyanenko (299-302).
The technology of solid-state modification of hyaluronic acid (HA) with sodium decahydroborate by deformation in Bridgman anvils was developed. The deformation was carried out at a pressure of 1 GPa and a rotation angle of 500°. The structure of the obtained complexes was studied. It was shown using Raman and IR-Fourier spectroscopy that HA and the polyborates could form a network of cyclic polymeric chelate complexes in which HA acted as a multidentate ligand. The biodistribution of the HA-based B-containing compound in organs and tissues of mice with B-16 melanoma was studied after a single intratumoral administration. The maximum B content in the tumor was observed 15 min after administration. However, it was halved after 1 h and decreased by 5 times by 3 h. The most opportune time for performing a boron-neutron-capture therapy session was 30 min after administration when the tumor B concentration was >30 μg/g and exceeded the content in surrounding tissues. The tumor/muscle and tumor/blood ratios reached 3 and 5, respectively. Use of this non-toxic compound for neutron-capture therapy was deemed promising based on preclinical studies.
Keywords: hyaluronic acid; 10B; Bridgman anvils; biodistribution; B-16 melanoma; neutron-capture therapy

Synthesis and Antitumor and Antibacterial Properties of New N-Alkylated Pyrimidines by A. A. Arutyunyan; S. S. Mamyan; H. M. Stepanyan; R. V. Paronikyan (303-306).
Uracil and 5-fluoro-, -bromo-, and -iodouracils were alkylated by substituted benzylchlorides to obtain N1-mono- and N 1,N 3-bis-substituted derivatives. The toxicity, antitumor, and antibacterial properties of the synthesized compounds were investigated. It was established that 5-fluoro- and 5-iodouracils exhibited more pronounced antitumor properties than 5-bromouracil derivatives.
Keywords: uracil; 5-halouracils; substituted benzylchlorides; alkylation; N 1-mono-substituted uracils; N 1,N 3-bis-substituted uracils; antitumor and antibacterial properties

Synthesis and Antimicrobial Activity of 2-Chloro(bromo)-(2-methyl)-3-arylpropionamides by B. D. Grishchuk; R. V. Symchak; V. S. Baranovskii; S. I. Klimnyuk; E. V. Pokryshko (307-309).
2-Chloro(bromo)-(2-methyl)-3-arylpropanamides exhibited low antimicrobial activity with respect to strains of staphylococci, intestinal rods, aerobic bacilli, and yeast fungi. Introduction of pharmacophores into the aromatic ring did not increase significantly the antibacterial and antifungal activity of these compounds.
Keywords: 2-chloro(bromo)-(2-methyl)-3-arylpropionamides; synthesis; antimicrobial activity

The influence of various blood substitutes on the physicochemical parameters of stable emulsions based on perfluorocarbons (PFCs) and phospholipids (PhLs) was studied. The particle structure, size, and surface properties in the emulsions did not change upon mixing with blood substitutes (0.9% NaCl, mafusol, polyoxidine, polyoxifumarin, and refortan). The relative viscosities of all mixed media did not exceed the values of this parameter for blood plasma. It was suggested that the PFC/PhL emulsion would perform in vivo a gas-transport function and would not produce negative effects on the blood viscosity.
Keywords: emulsions; perfluorocarbons; phospholipids; particle size and structure; stability; blood substitutes; blood serum; compatibility

A universal method for the synthesis of fatty aromatic, aromatic, and heteroaromatic acids that was based on carbonylation under mild conditions using catalysts based on modified cobalt carbonyl was developed and could be used for drug production.
Keywords: carbonylation; cobalt carbonyl; fatty aromatic; aromatic; heteroaromatic acids

Influence of various factors on the solubility of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymers in water by S. A. Kedik; A. V. Panov; V. V. Suslov; D. V. Eremin; T. E. Ivanova; J. V. Kochkina; G. O. Malinovskaya (318-320).
The water solubility of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymers with various monomer ratios was investigated. Aqueous solutions of the copolymers had low critical mixing temperatures. The water solubility of the copolymers decreased with increasing pH and concentration of 2-methyl-2-vinylpyridine monomers. Correlation dependences for predicting the concentration and pH range of the homogeneous solution at a given mixing temperature were determined. The results were useful for creating injection-ready drug forms based on N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymers.
Keywords: water solubility; copolymers; N-vinylpyrrolidone; 2-methyl-5-vinylpyridine

Quantitative Determination of the Peptide GB-115 in Biological Media by HPLC/MS by E. V. Ivannikova; S. S. Boiko; D. V. Bastrygin; V. P. Zherdev; T. A. Gudasheva (321-324).
A chromatographic method for quantitative determination of the peptide substance GB-115 with anxiolytic activity was developed. The optimum conditions for GB-115 extraction from biological materials were found. Quantitative determination was carried out using HPLC with mass-spectrometric detection. The detection limit of GB-115 was 1 ng/mL.
Keywords: GB-115; HPLC with mass-spectrometric detection; pharmacokinetics

Determination of lipid-soluble components in lutein forte by E. I. Finkelshtein; E. A. Belozertseva; E. V. Trifonova; V. I. Shvets (325-329).
An HPLC method for quantitative determination of lutein, zeaxanthin, retinyl acetate, and tocopheryl acetate in Lutein Forte was developed. The resolution of peaks as a function of two- and three-component mobile phases (MP) was studied. It was shown that Lutein Forte contained a third carotinoid in addition to the declared carotinoids lutein and zeaxanthin. An experimental planning method established that the optimum combination for efficient separation of lutein and zeaxanthin (R = 1.52) and analysis time (24 min) was MP composition CH3CH:dioxane:H2O 88:7:5. The contents of lutein, zeaxanthin, retinyl acetate, and tocopheryl acetate corresponded according to the quantitative determination results to those declared. The relative uncertainty of the average results was less than 1.28%.
Keywords: Lutein Forte; HPLC; quantitative determination; lutein; zeaxanthin; retinyl acetate; tocopheryl acetate

Development and validation of a GC-FID method for quantitation of impurities in kemantane drug substance by A. V. Tolkacheva; L. N. Grushevskaya; N. I. Avdyunina; B. M. Pyatin; V. I. Prokofeva; L. M. Gaevaya (330-336).
The objective of the study was to develop and validate a new GC-FID method for determination of impurities in kemantane (5-hydroxyadamantan-2-one) drug substance. The chromatographic mobilities of potential impurities in kemantane such as adamantan-2-one, adamantan-1-ol, adamantan-2-ol, adamantane-1,4-diol, adamantane-1,4-diol (syn-isomer), adamantane-2,6-diol, and adamantane-2,6-dione were studied. The chromatographic separation was performed on a quartz capillary column (VF-624ms, 60 m × 0.32 mm, 1.80 μm film thickness). The chromatographic system suitability parameters and method robustness factor were determined. The method had acceptable specificity, accuracy, linearity, and precision and high sensitivity. The developed method detected an impurity of adamantane-2,6-dione from 1.01 to 2.97% in four batches of kemantane drug substance.
Keywords: kemantane; drug substance; 5-hydroxyadamantan-2-one; adamantane-2,6-dione; adamantane derivatives; impurities; validation; gas-liquid chromatography; GC

It was found that a Nucleosil 100-5 OH column could be used for the analysis of platinum(II) coordination compounds. Use of mobile phases of CH3CN:H2O mixtures in ratios from 95:5 to 85:15 separated Pt(II) coordination compounds on chromatographic columns with diol and amine phases through a normal-phase mechanism.
Keywords: HPLC; oxaliplatin; carboplatin

Methods for determination by atomic absorption spectroscopy of toxic elements in shunlite active substance were developed. Use of shunlite as an enterosorbent was demonstrated to be promising.
Keywords: shunlite; toxic elements; adsorption capacity; enterosorbent; atomic absorption spectroscopy