Pharmaceutical Chemistry Journal (v.43, #10)

Prospects for the creation of new antiviral drugs based on glycyrrhizic acid and its derivatives (a review) by L. A. Baltina; R. M. Kondratenko; L. A. Baltina Jr.; O. A. Plyasunova; A. G. Pokrovskii; G. A. Tolstikov (539-548).
The review is devoted to the problem of creating new antiviral drugs based on glycyrrhizic acid (GA), the major triterpene glycoside extracted from roots of common and Ural licorice (Glycyrrhiza glabra L. and G. uralensis Fisher, respectively). Published data on the natural GA sources, antiviral activity of GA and its derivatives, clinical applications of GA-based drugs, and the properties of GA-containing biologically active nutrient additives are summarized. Possible mechanisms of the antiviral activity of GA and its derivatives are examined. It is shown that chemical modification of GA is a promising way of designing new highly active antiviral drugs for the prophylaxis and treatment of HIV, hepatitis B and C, corona-virus, and herpes simplex virus infections.
Keywords: licorice root; glycyrrhizic acid; antiviral activity; antiviral drugs; biologically active nutrient additives

Synthesis and cytotoxic activity of the products of heterocyclization of trifluoromethylcyanovinyl phosphonates by A. F. Shidlovskii; A. S. Peregudov; Yu. N. Bulychev; N. D. Chkanikov (549-559).
Heterocyclization reactions of trifluoromethylcyanovinyl phosphonates (TFMCPs) with aminopyrazoles, aminopyridines, amidines, and arylhydrazines have been studied. It is shown that TFMCPs can be used as precursors of 4,5-dihydropyrazolo[1,5-a]pyrimidines; 4,7-dihydropyrazolo[3,4-b]pyridines; 2H-pyrido-[1,2-a]pyrimidines; 1,4-dihydropyrimidines; 5-oxo-4,5-dihydro-1H-imidazoles; and 2,3-dihydro-1H-pyrazoles modified by both trifluoromethyl and diethoxyphosphoryl groups. The cytotoxic activity of some of the synthesized compounds and a series of fluorinated heterocycles obtained earlier from vinyl phosphonates has been investigated in vitro at the National Cancer Institute (USA) on a standard panel consisting of 60 human tumor-cell lines.
Keywords: 4,5-dihydropyrazolo[1,5-a]pyrimidines; 4,7-dihydropyrazolo[3,4-b]pyridines; 2H-pyrido[1,2-a] pyrimidines; 1,4-dihydropyrimidines; 5-oxo-4,5-dihydro-1H-imidazoles; 2,3-dihydro-1H-pyrazoles; cytotoxic activity; synthesis

An 11α-nitroxy group was introduced into 17α-ethynylestradiol-3,17-diacetate using a synthetic scheme involving oxidative nitration by cerium ammonium nitrate and configuration inversion at C11 by sodium-borohydride reduction of the 11-nitrate 9α,11β-dihydroxy derivative of the starting steroid. The 11α-nitroxy-containing ethynylestradiol exhibits antiestrogen activity.
Keywords: synthesis; oxidative nitration; antiestrogen

Synthesis and biological activity of water-soluble polymer complexes of arbidol by M. Yu. Eropkin; M. V. Solovskii; M. Yu. Smirnova; T. S. Bryazzhikova; T. M. Gudkova; N. I. Konovalova (563-567).
We have synthesized water-soluble complexes between the antiviral drug arbidol and polymer compounds with molecular masses of 19–31 kDa representing copolymers of acrylamide (AA) and 2-acrylamido-2-methylpropanesulfonic acid (AAMPS). The complexes are less toxic than arbidol and retain the high level of antiviral activity of this drug. The content of arbidol in the obtained complexes is within 26.4–32.1 mass%. The antiviral activity of the synthesized polymeric complexes against all studied viruses, including human epidemic influenza virus A (H3N2), bird highly pathogenic influenza virus A (H5N1), herpes type 1 virus (HSV-1), and adenovirus type III (AV-III) is comparable to the antiviral effect of nonmodified arbidol. The in vitro toxicity of the obtained complexes is about one order of magnitude lower than that of nonmodified arbidol; the pharmacological index, four times that of the initial low-molecular-weight drug. The synthesized water-soluble polymer complexes of arbidol can be useful in pharmacology since they can serve as the basis for new effective and safe parent antiviral substances and related formulations.
Keywords: water-soluble polymer complexes of arbidol; antiviral activity; use in pharmacology

Molecular design and targeted synthesis of N-substituted 4-oxo-1,4-dihydropyrimidine derivatives on the basis of inhibitory neurotransmitters by I. P. Kodonidi; E. T. Oganesyan; A. A. Glushko; I. N. Turenkov; V. V. Bagmetova; D. S. Zolotykh; A. V. Pogrebnyak (568-574).
A complex approach to the molecular design of a new class of neurotropic compounds on the basis of N-substituted 4-oxo-1,4-dihydropyrimidine is proposed. According to predictions, the 4-oxopyrimidine nucleus acts as the basic pharmacophore fragment while neurotransmitter amino acids and peptides are used as secondary pharmacophore fragments. On this basis, a set of N-substituted 4-oxo-1,4-dihydropyrimidine derivatives was synthesized. Initial pharmacological screening showed evidence for pronounced psychotropic activity of the synthesized compounds.
Keywords: molecular design; endogenous substances; neurotropic; psychotropic effect; prediction of biological activity; MSpace method; receptors

Technology for isolating estrogen preparation ferulen from Ferula tenuisecta roots by R. M. Khalilov; A. U. Mamatkhanov; L. D. Kotenko (575-578).
The possibility of isolating total esters (ferulen) from Ferula tenuisecta roots has been studied. Optimum conditions for extraction of ferulen are established. The results are used to develop a processing scheme for ferulen isolation. Quantitative determination methods for ferulen are proposed.
Keywords: ferulen; F. tenuisecta Eug. Korov.; quantitative determination

Quantitative determination of the sum of flavonoids in the new herbal preparation profem by T. V. Kornopol’tseva; G. V. Chekhirova; T. A. Aseeva (579-581).
A method for quantitative determination of the sum of flavonoids in the new herbal preparation profem (herbal tea and polyextract) has been developed with a view to standardization of the initial raw materials. Profem is based on the herbs of Panzerina lanata (L.) Sojak (Lamiaceae), shoots of Pentaphylloides fruticosa (L.) O. Schwarz (Rosaceae), and roots of Comarum palustre L. (Rosaceae).
Keywords: sum of flavonoids; quantitative determination; new herbal preparation profem

The possibility of using capillary electrophoresis was studied with the aim of improving the quality control and selecting the most objective quality criteria of chamomile flowers. It is established that an aqueous solution of sodium tetraborate with a concentration of 10 mg/mL should be used as the leading electrolyte and the separation can be performed at a voltage of 20 kV. Experiments showed that one of the main flavonoids in these herbs is apigenin-7-O-glucoside, the content of which varies from 0.17 to 0.36%.
Keywords: capillary electrophoresis; chamomile flowers; apigenin-7-O-glucoside

Obtaining new hydrophobic bases from various fats and oils for soft medicinal forms by Kh. M. Komilov; Ya. K. Nazirova; K. S. Makhmudzhanova (585-586).
New hydrophobic bases for suppositories and ointments have been developed using transesterification products of plant oils and animal fats under the action of lipolytic enzymes, in particular, lipase from cotton seeds. The possibility of using the obtained substances with surfactant additives in suppository and ointment formulations has been assessed. The quality characteristics of the new bases satisfy the requirements of regulations and allow their use in the technology of suppositories and ointments.
Keywords: suppository and ointment bases; transesterification method; lipolytic enzymes; soft medicinal forms

On the article about the component composition of Teraphthal preparation by O. L. Kaliya; E. A. Luk’yanets (587-587).