Pharmaceutical Chemistry Journal (v.43, #3)
Development of structure-toxicity relationship models of chemicals with respect to Guppy by O. A. Raevsky; V. Yu. Grigor’ev; O. V. Tikhonova (125-129).
Classification models are constructed using various methods of multidimensional data analysis for the discrimination of compounds with respect to four possible models of action (MOA) on Guppy. Classification models are also obtained for the discrimination of chemicals with general toxicity MOA and with polar narcosis MOA with respect to all other chemicals. Regression models are generated for the description of the toxicity of chemicals with nonpolar and polar narcosis MOA. In particular, a good two-parameter model based on molecular polarizability and proton-acceptor ability of molecules is proposed. A difference between the mechanisms of polar narcosis MOA and general toxicity MOA is identified. The proposed classification and regression models for the description of toxicity of chemicals with reactive and specific MOA are considered as formalized and preliminary. These models can be further improved by providing a more detailed structure description using not only 2D but also 3D descriptors.
Keywords: QSAR; toxicity; Guppy; HYBOT
Pharmacokinetics of acetaminophen administered in tablets and capsules under long-term space flight conditions by I. V. Kovachevich; S. N. Kondratenko; A. K. Starodubtsev; L. G. Repenkova (130-133).
The pharmacokinetics of acetaminophen in two medicinal forms, tablets and capsules, have been studied in healthy volunteers after single peroral administration at a dose of 500 mg under usual living conditions and during long-term space flight. The rate of drug absorption from tablets decreases significantly whereas the relative bioavailability increases substantially under microgravity conditions (compared with usual conditions). For the encapsulated medicinal form, the time of absorption decreases statistically reliably and the half-elimination time, the average retention time, and the distribution volume increase considerably whereas the bioavailability changes insignificantly.
Keywords: acetaminophen; tablets; capsules; pharmacokinetics; space flight
Synthesis and antimetastatic activity of metal complexes based on substituted pyridinecarboxylic acid amides and platinum tetrachloride by B. S. Fedorov; M. A. Fadeev; G. I. Kozub; S. M. Aldoshin; Z. G. Aliev; L. O. Atovmyan; N. P. Konovalova; T. E. Sashenkova; T. A. Kondrat’eva; S. V. Blokhina (134-138).
Previously unreported platinum tetrachloride derivatives have been synthesized via the interaction between dipotassium- and disodiumhexachloroplatinates with substituted amides of nicotinic and isonicotinic acid. The synthesized compounds exhibit low general toxicity and show high antimetastatic activity with respect to experimental melanoma B-16 and Lewis lung carcinoma strains.
Keywords: platinum tetrachloride derivatives; dipotassium hexachloroplatinate; disodium hexachloroplatinate; metal complexes; substituted amides of nicotinic and isonicotinic acids; melanoma B-16; Lewis carcinoma of lung; toxicity; metastasis
Synthesis and biological activity of condensed derivatives of thieno[3,2-d]thiazolo(thiazino, thiazepino)[3,2-a]pyrimidines by E. G. Paronikyan; Sh. F. Akopyan; A. S. Noravyan; G. A. Panosyan; G. M. Stepanyan; B. T. Garibdzhanyan; I. A. Dzhagatspanyan; I. M. Nazaryan; A. G. Akopyan (139-143).
Methods for the synthesis of new heterosystems including condensed pyrano[4′,3′:4,5]pyrido[2,3-b]-thieno[3,2-d]thiazolo(thiazino, thiazepino)[3,2-a]pyrimidines, thiazolo(thiazino, thiazepino)[3″,2″:1′,2′]pyrimido[4′,5′:4,5]thieno[2,3-c]isoquinolines, and cyclopenta[4′,3′:4,5]pyrido[2,3-b]thieno[3,2-d]thiazolo(thiazino)[3,2-a]pyrimidines are developed. The synthesis is carried out on the basis of 1-amino-2-ethoxycarbonylpyrano[4,3-d]thieno[2,3-b]pyridines and -thieno[2,3-b]isoquinolines. Antitumor and anticonvulsant properties of the synthesized products have been evaluated. Compounds possessing low toxicity and moderate biological activity are found.
Keywords: pyrano[4′,3′:4,5]pyrido[2,3-b]thieno[3,2-d]thiazolo(thiazino, thiazepino)[3,2-a]pyrimidine; thiazolo(thiazino, thiazepino)[3″,2″:1′,2′]pyrimido[4′,5′:4,5]thieno[2,3-c]isoquinoline; cyclopenta[4′,3′:4,5]-pyrido[2,3-b]thieno[3,2-d]thiazolo(thiazino)[3,2-a]pyrimidine; 1-amino-2-ethoxycarbonylpyrano[4,3-d]-thieno[2,3-b]pyridines and -thieno[2,3-b]isoquinoline
Synthesis and antibacterial properties of hydrazonothiazolyl derivatives of saturated 2,4,4-substituted butanolides by T. V. Kochikyan; E. V. Arutyunyan; M. A. Samvelyan; V. S. Arutyunyan; A. A. Avetisyan; R. V. Paronikyan; G. M. Stepanyan (144-147).
A method has been developed for the synthesis of new heterocyclic compounds containing γ-butanolide fragments. The antibacterial properties of the obtained compounds have been investigated. The tested compounds exhibit moderate antibacterial activity.
Keywords: synthesis; thiazolyl- and triazolyl lactone derivatives; indolyllactones; ketolactone thiosemicarbazones; antibacterial activity
Synthesis, molecular docking, and biological testing of new selective inhibitors of glycogen synthase kinase 3β by E. A. Ryzhova; A. G. Koryakova; E. A. Bulanova; O. V. Mikitas´; R. N. Karapetyan; Ya. V. Lavrovskii; A. V. Ivashchenko (148-153).
The synthesis, molecular docking, and biological testing of a series of new heteroaryl-substituted oxadiazole-5-carboxamide inhibitors of glycogen synthase kinase 3β (GSK-3β) are described. The synthesis includes several stages and is based on the advanced liquid-phase combinatorial approach. Molecular docking was used for the rational selection of synthesized compounds for the subsequent biological testing. It is established that the inhibitory activity of the synthesized compounds strongly depends on the character of substituents in the phenyl ring and the nature of terminal heterocyclic fragments. The most active compounds inhibit GSK-3β at IC50 in the micromolar range and can be considered as potential drug candidates.
Keywords: GSK-3β; synthesis; molecular docking; biological testing
Triacylglycerols of the lipid fraction from fruits of two Echinacea species by V. V. Vandyshev; E. Yu. Babaeva; D. D. Drozdovskaya (154-156).
Fatty oils extracted from the fruits of Echinacea purpurea and E. pallida species have been analyzed. The extracts represent oily and readily mobile light yellow liquids. Fruits of E. purpurea contain 33.6% fatty oil; of E. pallida, 23.2%. NMR spectroscopy analyses of fatty oils from fruits of the two Echinacea species show that these substances belong to liquid plant oils such as linoleic acid, which is confirmed by the measured numerical indices.
Keywords: Echinacea ; linoleic acid; method of extracting
Standardization of inulin extracted from Dahlia single tubers and some physicochemical properties of inulin by N. A. Anan´ina; O. A. Andreeva; L. P. Mycots; E. T. Oganesyan (157-159).
Inulin extracted from Dahlia single L. tubers has been standardized. Procedures for the quantitative determination of the main substance (inulin) and bound glucose have been developed. Their contents are 95.72±1.05% and 4.38±0.85%, respectively. Some physicochemical properties of inulin, including surface activity, micelle formation ability, and solubilization ability, have been studied.
Keywords: Dahlia single L. tubers; inulin; standardization; surface activity; micelle formation ability; solubilization
Technology for cinaroside production from the aerial part of Ferula varia and evaluation of its hypoazotemic activity by M. A. Mamatkhanova; R. M. Khalilov; V. N. Syrov; A. U. Mamatkhanov; L. D. Kotenko; G. B. Satimov; Sh. N. Madrakhimov (160-162).
The optimal regime of cinaroside extraction from the aerial part of Ferula varia has been found. Aprocessing scheme for obtaining cinaroside has been developed on the basis of these data. Two samples of cinaroside (obtained by the laboratory and semi-industrial methods) are comparable to the well-known medicinal preparation lespenephryl with respect to hypoazotemic action. This fact indicates that Ferula varia is a valuable source of cinaroside. A technology has been developed for producing a new medicinal form of cinaroside in 0.05 g tablets.
Keywords: Ferula varia ; cinaroside; medicinal form; extraction
Nanosized forms of drugs (A Review) by G. V. Nazarov; S. E. Galan; E. V. Nazarova; N. N. Karkishchenko; M. M. Muradov; V. A. Stepanov (163-170).
The main directions of research in the field of nanosized carrier systems for targeted delivery of drugs are reviewed. The fields of research and the results from characterization of the pharmacological properties of nanosized forms of drugs, including nanospheres, liposomes, dendrimers, fullerenes, nanocapsules, and nanocrystalline forms of drugs are considered. Prospects of the search for new forms of drugs based on achievements in nanobiotechnology are considered with a view to the reduction of side effects and improvement of the bioavailability of drugs.
Keywords: drugs; nanosized forms; targeted delivery of drugs
Evaluating the pharmaceutical equivalence of drugs in the registration stage by A. V. Korolev; T. N. Bokovikova; A. I. Luttseva; S. E. Milkina; E. B. Nechaeva; N. P. Sadchikova (171-175).
Comparative data on the dissolution kinetics profiles of more than 200 drug pairs have been analyzed. It is shown that the comparative dissolution test provides effective evaluation of the pharmacological equivalence during preclinical trials of generic drugs and the drugs with claimed changes in composition in the registration stage.
Keywords: dissolution test; pharmaceutical equivalence; generic drug
Using HPLC with mass-spectrometric detection for riboflavin determination in complex medicinal forms by D. A. Mitrofanov; G. V. Nazarov; I. Yu. Babkin; S. E. Galan; V. M. Goncharov; S. V. Vostrukhov (176-179).
A method for determining riboflavin in complex medicinal forms is developed and makes use of an HPLC with mass-spectrometric detection and electrospray ionization (HPLC/MS-API-ES). Conditions of sample preparation for the analysis of riboflavin with a sensitivity of 1 × 10 –5 mg/mL are optimized. The proposed technique has been checked using the “introduced-found” approach. The technique is successfully used for the analysis of commercial vitamin-mineral complexes.
Keywords: riboflavin; vitamin-mineral complexes; HPLC/MS electrospray ionization