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Vol 22, No 7 (2019)
- Year: 2019
- Articles: 9
- URL: https://journals.eco-vector.com/1560-9596/issue/view/5706
Articles
Synthesis of the pharmacologically active analog of the GSB-106, DIPEPTID mimetic of BDNF
Abstract
Previously the dimeric dipeptide mimetic bis-(N-monosuccinil-L-seryl-L-lysine) hexamethylenediamide (GSB-106) was created in Zakusov Institute of Pharmacology. GSB-106 demonstrates neuroprotective activity in vitro under oxidative stress conditions in concentrations of 10-5-10-7 M and also it demonstrates antidepressant activity in behavioral tests in rodents i.p. in the doses of 0.1-1.0 mg/kg. The acetyl analog of GSB-106, bis-(N-acetyl-L-seryl-L-lysine) hexamethylenediamide (GTS-106Ac), was synthesized to study the role of the N-acyl radical in the activity of the GSB-106. The study of the neuroprotective activity of GTS-106Ac on the neuronal HT-22 culture under conditions of oxidative stress showed this activity in concentrations of 10-5-10-8 M. In the test of Porsolt in mice, i.p., GTS-106Ac showed the antidepressant effect in the doses of 1.0 and 5.0 mg/kg, significantly reducing the time of immobility of the animals compared with control group of animals. Thus, the replacement of the monosuccinyl radical with the acetyl one in the structure of GSB-106 leads to the increasing of the neuroprotective effect, but to the decreasing of the antidepressant effect.
Problems of Biological Medical and Pharmaceutical Chemistry. 2019;22(7):3-9
3-9
Uvazhaemyy chitatel'!
Problems of Biological Medical and Pharmaceutical Chemistry. 2019;22(7):10-10
10-10
Metabolomics of the genus Penicillium fungi
Abstract
The metabolome of the 113 Penicillium fungi strains isolated from various habitats were investigated, including from the permafrost of the Arctic and Antarctic. In polyphasic taxonomy, the new system that has been used in recent years to identify the fungi of the genus Penicillium, secondary metabolite profiles are applied together with the micro- and macro-morphological characteristics of the strains. The species identification of penicillae by morphological features, isolated from natural substrates, is often difficult. For example, in fresh isolates from low-temperature ecotopes, a shift of temperature growth optimum is observed toward lower temperatures compared with typical strains. Therefore, the metabolite profiles obtained using metabolomic are the easiest way to obtain informative data that can be used for the purposes of the taxonomy of fungi. As a result of screenings, profiles of secondary metabolites were successfully applied to the species identification of strains. Some strains isolated from modern habitats had a more complete spectrum of diagnostic secondary metabolites compared with strains isolated from permafrost from 15 to 600 thousand years old. For example, 10 strains of P. commune, isolated from ancient Arctic sediments, synthesized only CPA, and 7 strains, isolated at cheese-making factory, formed CPA and rugulo-vasines. New producers of biologically active compounds were found which may be promising for drug biotechnology. The production of mycophenolic acid, which is used as an immunosuppressive agent, is found in the strains of P. brevicompactum and P. roqueforti.
Problems of Biological Medical and Pharmaceutical Chemistry. 2019;22(7):11-25
11-25
Metabolic profiling of Artemisia santhonicum and Artemisia lerchiana by GC/MS
Abstract
In the flora of Bulgaria, the genus Artemisia L. is represented by 13 species. This study is devoted to the study of two morphologically similar species - Artemisia lerchiana Stechm and Artemisia santonicum L. Materials and methods. The objects of study were methanol and acetone extracts from the dried aerial part and the fractions obtained from them. We used TLC and GC-MS methods. The antioxidant activity of the extracts was assessed by the method with DPPH reagent. Results and discussion. In the lipophilic fractions of the methanol extract of A. lerchiana and A. santonicum fatty acids, higher alcohols and sterols was found, and A. santonicum is distinguished by a high content of C18:3, C18:1, C18:2 fatty acids. Organic acids, phenolic acids, mono- and disaharas were found in the polar fractions. In the acetone extract triterpenes, organic and phenolic acids, and sugars were determined. Using TLC profile differences for the studied species were established. When comparing the antioxidant properties, it was found that the methanol extracts of the studied species have the greatest activity compared to the acetone extracts, while the extracts from A. santhonicum exhibited stronger activity than A. lerchaina. Findings. A comparative study of the profile of the metabolites of A. santhonicum and A. lerchaina was carried out. It has been shown that the methanol extract of A. santhonicum has a richer metabolite composition and a higher antioxidant activity. The data obtained are new to the studied representatives of the genus Artemisia L.
Problems of Biological Medical and Pharmaceutical Chemistry. 2019;22(7):26-26
26-26
Comparative study of the contents of main classes of phenolic compounds in roots and rhizomes of Potentilla alba, Potentilla recta and Potentilla anserine
Abstract
The principal aim of the study was a comparative quantitation of the main classes of phenolic compounds (PC): gallo-and ellag-itannins, procyanidins and prodelphinidines, p-coumaroyl and caffeoyl-derivatives of quinic acid, as well as kaempferol-, quercetin- and myricetin-glycosides, in the roots and rhizomes of Potentilla recta, Potentilla anserina and Potentilla alba. For analyzing plant PC was applied an ultra-efficient liquid chromatography combined with diode detector and high-resolution mass spectrometry. Content of various classes of PC was determined with application of multiple reaction monitoring (MRM) method. As a result, it was shown that the roots and rhizomes of the P. alba contain about 7,3% of procyanidins, but this species did not contain hydrolyzable tannins and other classes of PC. P. recta differs in approximately equal content of hydrolyzable and condensed tannins, but content of procyanidins was almost 2 folds less than that in P. alba. An even smaller amount of PC was found in the roots of P. anserina. At the same time, P. anserina was characterized by a significantly higher content of prodelfinidins, then procyanidins, which were typical for the other two species, P. alba and P. recta.
Problems of Biological Medical and Pharmaceutical Chemistry. 2019;22(7):27-31
27-31
The method of obtaining affects on the composition of polysaccharides Saussurea controversa DC. and their no-stimulating activity
Abstract
Plant PSs can change the production of nitric oxide by macrophages. To assess the PSs biological activity, independent of contained impurities, purification is required. Purpose. Identify the relationship between the method of obtaining WSPSs from leaves of Saussurea controversa and their ability to stimulate NO-production by mouse peritoneal macrophages. Methods. WSPSs was obtained by extraction with cold (PS1) and hot water (PS2) after pretreatment, extraction with 40% aqueous ethanol (PS3) and with acidified by hydrochloric acid water from raw materials (PS4). The biological activity of WSPSs was studied in C57BL/6 male mice through the NO-production by macrophages using Grace reagent and their proliferation using MTT. The impurity of endotoxin in the samples was determined in a test with antibiotic polymyxin B. Results. The derived WSPSs varied in protein content, uronic acids and monomeric composition. PS2 and PS3 did not affect the viability of macrophages; PS1 and PS4 reduced proliferation relative to intact cells, and PS1 in comparison with LPS. All samples enhanced the nitrites production by macrophages. The suppression of NO-production was detected in cultivation with PS2, PS3 and PS4 treated by polymyxin B. The NO-production during cultivation with PS3, was completely determined by endotoxin. Incubation of polymyxin B with PS1 did not affect its NO-activating properties. Conclusions. Extraction with cold water allows to isolate PSs, free from impurities, with NO-stimulating activity independent of endotoxin, which are promising therapeutic substances for further research of biological activity.
Problems of Biological Medical and Pharmaceutical Chemistry. 2019;22(7):32-37
32-37
Composition of essential oils of Origanum vulgare L. varieties from VILAR collection
Abstract
Origanum vulgare L. varietal plants belong to certain morphotypes, characterized by a genetically fixed complex of constant features (height, color of organs, type of growth, biometric indicators). Determined the structure and content of individual compounds of essential oil of three varieties of O. vulgare ('Raduga', 'Slavnitca', 'Zima') the biological collection of VILAR. T. EO analysis was performed by gas chromatography and mass spectrometry (GC-MS). As a result, 120 individual compounds were found in the composition of O. vulgare EO and 62 compounds were identified. The main compounds of EO are the 11 compounds: terpinene-4-ol (16.4%), p-caryophyllene (12.4%), germacrene D (9.7%), caryophyllene oxide (8.2%), spathulenol (7.7%) and a-cadinol (6.0 %), Y-terpinene (2.9%) and 6-cadinol (2.8%) and a-humulen (2.2%), 6-cadinene (1.9%) and a-terpineol (1.7%). They account for 71.9% of the total content of EO compounds. Compounds from the group of sesquiterpenes predominate in all varieties, but their maximum content was found in the variety 'Zima' (51%). The variety 'Slavnitca' the content of compounds monoterpenes 6 times more than the variety 'Raduga' and 14 times more than the variety 'Zima'. The highest content of phenolic compounds was found in the 'Raduga' variety. The results suggest the presence of O. vulgare varietal chemotypes not only in connection with the content of phenolic components (thymol and carvacrol), but also in connection with the total content of compounds of other groups (monoterpenes and sesquiterpenes), characterized by specific pharmacological activity. All varieties of O. vulgare are related to low-phenol chemotypes (thymol and carvacrol content was less than 1%).
Problems of Biological Medical and Pharmaceutical Chemistry. 2019;22(7):38-49
38-49
Variability of the Genus Thymus L. in gene bank of Slovak Republic
Abstract
In Slovakia found 28 species and 3 subspecies of the genus Thymus. Most genetic resources are the following species: T. pulegioides, T. praecox, T. pannonicus, T. capitata, and T. vulgaris. The aim of this study was to compare the genetic resources of the Thymus pulegioides L. samples, which were collected from different regions of Slovakia and the Czech Republic, stored in the Gene Bank of Slovakia. The evaluation of samples took five years 2009-2013. The size of the experiment was 3x30 m, genetic sources were planted in rows, 3 m each. The international descriptor (UPOV Thymus vulgaris L., 2002) was used for the evaluating of the morphological traits. The aerial parts of the plants have been harvested manually at the time of early flowering (June - July). Harvested material was dried at the room temperature of approximately 35 °C. Essential oil was isolated using very common method of steam distillation and the constituents of essential oil were analysed using GC-MS. The determinations were carried out according to the European Pharmacopoeia 8th edition (Ph. Eur. 8). The content of THD was determined using a colorimetric method with the Arnow reagent at 505 nm. The percentage contents of Total hydroxycinnamic derivatives (THD) were calculated and expressed as rosmarinic acid. As a result, from a morphological point of view, it was found that the diameter of the plant during cultivation reached 450-899 mm, stem length varied from 125 mm to 261 mm. The leaf blade length was measured in the 7.5-12.2 mm interval and the leaf blade width was from 4.6 mm to 7.5 mm. The coefficient of drying of raw materials interval was found 2.7-3.92. The content of THD expressed as rosmarinic acid varied from 2.11 to 8.0%. Was detected 5 linalool chemotypes, 2 geraniol-citral chemotypes, 1 geraniol chemotype, 5 car-vacrol chemotypes and 3 thymol chemotypes for T. pulegioides by the component composition of essential oil. This study confirmed high diversity of Thymus genus according to origin area, as well as morphological and phytochemical diversification within the species T. pulegioides due to the differences in the conditions of growing places.
Problems of Biological Medical and Pharmaceutical Chemistry. 2019;22(7):50-50
50-50
Study of acute toxicity of dry extract of Potentilla alba L
Abstract
Purpose. Determine the toxicity parameters of the dry extract of Potentilla alba L. when administered once to laboratory animals. Methods. The acute toxicity of the dry extract of Potentilla alba L. has been studied in BALB/c mice and Wistar rats of both sexes by intraperitoneal and intragastric administration. Toxicity parameters had determined by the method of Litchfield and Wilcoxon. Results. With a single intraperitoneal injection of the dry extract of Potentilla alba L. mice and rats (males and females), the same type of acute intoxication had observed: motor agitation, grooming, shortness of breath, cyanosis of the auricles and tail. The first death of animals had registered for 2-3 days after administration of the extract and continued for the next two days. The following indicators of average lethal doses for intraperitoneal administration to mice had established: 160 ± 26 mg/kg (males) and 150 ± 30 mg/kg (females), rats - 260 ± 45 mg/kg (males) and 250 ± 68 mg/kg (females). With a single injection of the dry extract of Potentilla alba L. in the stomach, the LD50 indice for mice and rats increase 40-50 times as compared with intraperitoneal administration and amount to 10,700-12,000 mg/kg for rats and 7,600-8,300 mg/kg for mice. Conclusion. With a single intraperitoneal and intragastric administration to laboratory animals (mice, rats of both sexes) of the dry extract of Potentilla alba L. is of low toxicity.
Problems of Biological Medical and Pharmaceutical Chemistry. 2019;22(7):51-54
51-54