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卷 26, 编号 4 (2023)

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Medical chemistry

Changes in the activity of lysosomal cysteine proteases in vascular wall homogenates in varicose veins of the lower extremities

Konopleva M., Gazaryan Z., Kalinin R., Suchkov I., Korotkova N.

摘要

Relevance. The article deals with the issue of changes in the activity of lysosomal cysteine proteases – cathepsins L, B, H in homogenates of vascular wall, obtained from patients with varicose veins of the lower extremities. Due to the fact that the proteolytic processes occurring in the wall of varicose transformed veins currently remain poorly understood, and the incidence of varicose veins is increasing, the relevance of the topic remains at a high level.

Materials and methods. The study shows the results from 22 patients divided into two groups: the first group (n=12): patients with varicose veins of the lower extremities, the second group (control) – patients who had healthy vein sections, taken during femoral-popliteal bypass surgery using autovena (n=10). The material for the study was homogenates of vascular wall, obtained during surgical intervention. The vessels were weighed on electronic scales (Ohaus corporation, USA). The samples were crushed and placed in a glass of the Potter S homogenizer (Sartorius, Germany). Homogenized for 60 seconds with a rotation speed of a Teflon pestle of 1500 rpm. The activity of cathepsins B, L and H was determined spectrofluorimetrically on the RF – Zhimadzu Spectrofluorometer (Japan). The protein content was assessed using the Lowry method by the commercial set of the NPC "Eco-service" (St. Petersburg).

Results. The activity of cathepsin B in the homogenate of varicose veins was increased by 35 times compared to the control group. The activity of cathepsin D in the homogenate of varicose veins was also increased 17-fold compared to the control. The activity of cathepsin H in varicose vein homogenate showed a unidirectional trend - it was higher than the control values, but by a smaller number of times – by 9. Thus, in varicose vein homogenates, all three studied cathepsins increase their activity, but to varying degrees. The greatest changes, according to our study, confirmed the activity of cathepsin B.

Conclusions. Varicose veins of the lower extremities are accompanied by a significant increase in the activity of lysosomal cysteine proteinases – cathepsins B, L and H in the wall homogenates of the affected vein, which may indicate the involvement of LC in the pathogenesis of venous transformation.

Problems of Biological Medical and Pharmaceutical Chemistry. 2023;26(4):48-53
pages 48-53 views

Pharmaceutical chemistry

Fruits of vegetable euterpe as a valuable source of food and biologicaly active compounds (review)

Kurdyukov E., Mitishev A., Vodopyanova O., Moiseeva I., Finaenova N.

摘要

Vegetable euterpe (Euterpe oleracea) belongs to the Arecaceae family, grows in tropical and subtropical areas. The people call the fruits of acai. Of the wild species of Brazil, the most important are Euterpe oleracea, Euterpe edulis and Euterpe precatoria. A botanical description, a review of the chemical composition of secondary metabolites, a description of the biological and pharmacological activity of Euterpe oleracea are presented. The main biologically active compounds are anthocyanins (cyanidin–3-O-glucoside, cyanidin-3-O-rutinosideo), flavonoids (quercetin, rutin), tannins (catechin, gallic acid), phenylpropanoids (chlorogenic acid), carotenoids (α-carotene, β-carotene). There is evidence of antioxidant, vasodilating, anti-atherosclerotic, anti-inflammatory, neuroprotective and antitumor activity. A wide variety of biologically active compounds that cause a multidirectional pharmacological effect in this plant makes vegetable euterpe a promising object for the development of pharmaceutical substances.

Problems of Biological Medical and Pharmaceutical Chemistry. 2023;26(4):3-9
pages 3-9 views

Relationship between biochemical indicators and phenotypical features of garden savory (satureja hortensis l.)

Malankina E., Solopov S., Romanova N.

摘要

Relevance. Garden savory (Satureja hortensis L.) is an annual medicinal plant of interest due to the content of essential oil and phenolic compounds, the content of which varies depending on the variety. Identification of the relationship between morphological and biochemical traits will make the selection of productive plants more effective and accelerated.

The purpose of the study is to identify the phenotypic characteristics of garden savory plants, indicating a high content of certain pharmacologically significant compounds or their groups.

Materials and methods. The 9 samples of garden savory served as the object of the study. The content of essential oil was determined in dry raw materials by hydrodistillation according to Clevenger, the component composition was determined by gas chromatography. The flavonoid content was determined in terms of rutin was carried out in terms of rutin, the amount of phenolic compounds and tannins in terms of gallic acid.

Results: Early maturing varieties are characterized by a high content of essential oil (r = 0.685) with a low content of tannins
(r = –0.69). There was a relationship between the leaf index and the content of tannins (r = 0.620), with the accumulation of flavonoids (r = –0.522), with the content of γ-terpinene in the essential oil (r = 0.77) and of carvacrol (r = –0.76).

The presence of anthocyanin coloration is interconnected with the content of essential oil (r = –0.688) and content of carvacrol in it
(r = –0.53), with the content of the sum of flavonoids (r = 0.598), gamma terpinene (r =0.541) and tannins (r = 0.7).

Conclusion. The identified phenotypic features of garden savory plants indicate a high content of certain pharmacologically significant compounds or their groups. Thus, is shown the selecting possibility of prospective plants according to external features.

Problems of Biological Medical and Pharmaceutical Chemistry. 2023;26(4):10-15
pages 10-15 views

Evaluation of dopaminergic activity of biologically active substances of verbena herb (verbena officinalis l.)

Kulyak O., Adamov G., Radimich A., Lupanova I., Saybel O.

摘要

Relevance. The development of herbal medicines remains relevant today. Verbena officinalis L. has a spectrum of pharmacological activity, but our interest is manifested in its ability to treat amenorrhea and anovulation in hyperprolactinemia.

The purpose of the work was to study the dopaminergic activity of the extract, fractions and dominant substances of the verbena officinalis herb.

Materials and methods. The object of the study is the verbena officinalis herb, harvested experimentally in the field of the Botanical Garden of the Federal State Budgetary Scientific Institution VILAR in 2019.

Results. The dopaminergic activity of fractions of different polarity of herb verbena officinalis was assessed. The most active absorb ethyl acetate fraction, which includes: verbenalin and verbascoside. Verbenalin has been found to have a dopaminergic effect. Dopaminergic activity of the total extract, ethyl acetate fraction and inflammation verbenalin.

Conclusions. It is expedient to develop drugs for the treatment of amenorrhea and anovulation based on a total extract standardized for verbenalin.

Problems of Biological Medical and Pharmaceutical Chemistry. 2023;26(4):16-22
pages 16-22 views

Novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives as promising compounds for the therapy of alzheimer's disease

Pozdnyakov D., Chiryapkin A., Kodonidi I.

摘要

Relevance. Alzheimer's disease is one of the most common forms of dementia with a high mortality and disability rate. Some quinazolinone derivatives having methoxy groups in the quinazolinone scaffold may be potentially effective agents for the treatment of Alzheimer's disease.

The aim of the study. To evaluate the effect of new derivatives of 6,7-dimethoxyquinazoline-4(3H)-one on the activity of acetylcholinesterase and the aggregation of amyloid particles process under experimental conditions

Materials and methods. The studied derivatives of 6,7-dimethoxyquinazoline-4(3H)-one with amino acid and dipeptides residues were obtained by replacing the oxygen heteroatom in the benzoxazinone core by boiling the initial compound with the corresponding amino acid. The anticholinesterase activity of the studied compounds was evaluated using an Ellman reagent with spectrophotometric detection of degradation products of 5.5'-dithiobis-2-nitrobenzoic acid. The antiamyloid activity of 6,7-dimethoxyquinazoline-4(3H)-oh derivatives was determined by a change in the intensity of aggregation of β-amyloid particles (fragment 1-42) with congo red. All tests were performed three times.

Results. As a result of the study, it was found that derivatives of 6,7-dimethoxyquinazoline-4(3H)-oh inhibit the activity of acetylcholinesterase in vitro with IC50 values in the range of 1.8±0.36 mg/ml to 4.2±0.96 mg/ml, which corresponded to the indicators of the referent - donepezil (IC50 = 2.4±0.06). It is also worth noting the presence of moderate antiamyloid properties of the studied substances, which reduced the aggregation of β-amyloid particles by more than 50%, which, however, was lower than the indicators of the referent - GV-791 (p<0.05). Among the studied substances, the highest level of activity was characterized by substances containing glycylglycine and glycylleucine residues in the structure, surpassing donepezil (p<0.05) in the ability to inhibit acetylcholinesterase.

Conclusion. The study showed that derivatives of 6,7-dimethoxyquinazoline-4(3H)-one with amino acid and dipeptides residues, in particular with fragments of glycylglycine and glycylleucine, can be promising objects for further development of drugs for the treatment of Alzheimer's disease with a predominant effect on acetylcholine metabolism.

Problems of Biological Medical and Pharmaceutical Chemistry. 2023;26(4):23-27
pages 23-27 views

X-ray fluorescence determination of silver in colloidal solutions

Kolyabina E., Maksimova T., Pleteneva T., Syroeshkin A.

摘要

Objective. To develop the basics of technology for X-ray fluorescence determination of silver in colloidal solutions.

Relevance. Silver preparations are interesting as an alternative to antibiotics. Сurrently on the pharmaceutical market there is a large number of silver-containing colloidal dietary supplements, 70% of which contain silver in ionic form. The energy dispersive method of X-ray fluorescence analysis is an express method without long-term sample preparation.

Materials and methods. Silver proteinate (~8% Ag), Sigma-Aldrich; ProtargolLor (P.J.S.C. “Pharmstandard”, Kursk); Sialor (J.S.C. RENEWAL®); Argitos colloidal silver (“Nanosphere”, Russia), Argent Colloidal (Nutri expert, France). Dual Laser Light Scattering 2D-DLS (Zetasizer Malvern). Energy dispersive spectrometer Shimadzu EDX-7000 (Japan); OriginLab Corporation, USA.

Results. The technology of the X-ray fluorescence determination of silver in colloidal solutions from various companies was described in this paper. The present study has exploited the energy dispersive spectrometer Shimadzu EDX-7000 (Japan). The fluorescence intensity at AgKα = 22.105 keV depends linearly on the silver concentration in the range of 0.01% - 1% according to the equation I = (5.1 ± 0.1) · СAg for silver nitrate and I = (1.64 ± 0.03) · CAg for silver proteinate, which is due to the effect of the organic matrix.

Conclusion. The new XRF method was applied for quality control of protargol and other Ag-containing drugs and parapharmaceuticals.

Problems of Biological Medical and Pharmaceutical Chemistry. 2023;26(4):28-31
pages 28-31 views

Development and validation of HPLC-MS/MS method for molsidomine quantitation in various tissues of rats

Popov N., Balabanyan V., Baranov N.

摘要

Relevance. Molsidomine is a vasoactive drug from the group of sydnonymines widely used in clinical practice. The use of molsidomine as a comparison drug during pharmacokinetic studies of new pharmacological agents of the sidnonymine group requires the development and implementation of accurate and reproducible methods for the quantitative determination of this drug in the organs and tissues of experimental animals.

Purpose of the study. Development and validation of a method for quantitative determination of molsidomine in various rat tissues using HPLC-MS/MS.

Materials and methods. Quantitative determination of molsidomine in blood plasma and homogenates of rat tissues was carried out by high-performance liquid chromatography with mass spectrometric detection. Method of precipitation of proteins with methanol was applied as a sample preparation of biological material. An Agilent Infinity LabPoroshell 120 EC-C18 4.6x100 mm 2.7 Micron column was used for chromatographic separation using an aqueous solution of methanol.

Results. The developed bioanalytical method was validated according to the following parameters: selectivity, matrix effect, sample transfer, linearity of the analytical range, lower limit of quantitative determination (NPCO), intra- and inter-series accuracy and precision, dilution factor, stability of the studied substances at the stages of analysis.

Conclusion. A method of quantitative determination of molsidomine in blood plasma and homogenates of rat tissues has been developed and validated. The analytical range for blood plasma, liver, kidney, brain and spleen homogenates was 5.0–1000.0 ng/ml; for skeletal muscle and heart tissue homogenates was 1.0-1000.0 ng/ml; for adipose tissue homogenate was 10.0–1000.0 ng/ml. This study allows us to use the developed methodology for conducting the analytical part of pharmacokinetic studies of molsidomine.

Problems of Biological Medical and Pharmaceutical Chemistry. 2023;26(4):32-42
pages 32-42 views

Harmonization of determination by thin-layer chromatography of the main groups of bas in medicinal plant raw materials of the republic of Tajikistan with the requirements of the state budget of the Russian Federation XIV edition

Sakhratov V., Malkova T., Uglovskaya A., Karpova L.

摘要

Relevance. The quality of medicinal plant raw materials is a necessary condition for its suitability for use along with safety. The appearance of impurities or the loss of biologically active substances during improper harvesting and storage negatively affect the pharmacological and physico-chemical properties. The regulatory framework for the evaluation of medicinal plant raw materials (LRS) in the Republic of Tajikistan includes the use of the USSR State Pharmacopoeia (GF) of the 11th edition, in the articles of which there is no section for determining the main groups of biologically active substances (BAS). Currently, the State Budget of the Russian Federation XIV has established a methodological approach for determining the main groups of BAS by thin-layer chromatography (TLC), which is economical, express and can be recommended for use in routine analytical practice of chemical laboratories of the Republic of Tajikistan for the purposes of input control of raw materials. Therefore, it is extremely important to harmonize the methodological basis for assessing the quality of the LRS of the Republic of Tajikistan with the requirements of the State Budget of the Russian Federation XIV.

The purpose of the work is to introduce into analytical practice the methodology for determining biologically active substances in plant raw materials produced and/or sold in pharmacy institutions of the Republic of Tajikistan by harmonizing and improving the methods of the State Budget of the Russian Federation XIV.

Materials and methods. The objects of the study were motherwort grass (Leonurus spp.), horsetail (Equisetum arvense), nettle leaves (Urtica dioica), thyme grass (Thymus serpyllum), representing LRS in cardboard packs purchased in pharmacies of the Republic of Tajikistan. It was not possible to determine the origin of raw materials (wild or cultivated) in these objects. Plates for Sorbfil PTSH-P-V-UV thin-layer chromatography were used as the stationary phase. The conditions of sample preparation, chromatography, and interpretation of the results obtained were optimized taking into account the current pharmacopoeia articles of the State Budget of the Russian Federation XIV.

Results. The harmonization of methods for determining the main groups of BAS of horsetail grass, motherwort, thyme, nettle leaves growing in the Republic of Tajikistan by thin-layer chromatography was carried out. Methodological recommendations have been developed.

Conclusions. The thin-layer chromatography method, due to its accessibility, cost-effectiveness and low time spent on analysis, can be widely used in the Republic of Tajikistan for the purposes of input and sample control of raw materials.

Problems of Biological Medical and Pharmaceutical Chemistry. 2023;26(4):43-47
pages 43-47 views

Anniversaries and dates

Obituary

Problems of Biological Medical and Pharmaceutical Chemistry. 2023;26(4):55
pages 55 views
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