The derivatives of 1,2,4-triazole are of the great scientific interest in the fields of pharmaceutics, agricultural chemistry, and construction The production of Trifuzol-Neo has already been launched, and it is now commercially available. Compounds based on 1,2,4-triazole may also be useful in veterinary practice due to their antiviral activity. Trifuzol-Neo, or piperidinium ([5-(2-furanyl)-4-phenyl-4Н-1,2,4-triazol-3-yl]thio)acetate (Figure 1), has already proved to be an effective immunostimulator for poultry.Since that, the quality control of raw materials and the ready product is required during the production stage. Currently, there is only one method for determination of the assay of Trifuzol-Neo, which involves HPLC-DMD (Center of Medical Research Information and Patent and Licensing Practice of Ukraine. The main disadvantages of HPLC-DMD are the use of relatively high amounts of costly solvents (acetonitrile in this case), considerable baseline instability, and time-consuming system stabilization. Gas-chromatography is able to avoid these constrictions since it involves gas as a mobile phase, which is a more cost-effective and reproducible alternative. The newly developed GC/MS method for Trifuzol-Neo assay determination consists of the following steps: weighing 20.0mg of Trifuzol-Neo powder, dillution in 20mL methanol, injection of 0.5uL of the obtained solution to GC column (at least three times). The same operations are done with a Trifuzol-Neo standard.
The genus Salvia L. has more than 900 species distributed throughout the globe. 21 species are growing in Ukraine. All species of this genus have essential oils. Salvia officinalis and Salvia sclarea have been used in the culture and are widely used in medical practice. The chemical composition of other species of sage and the possibility of their use in pharmaceutical and medical practice are almost not studied. Taking into account the results of chemotaxonomic studies of species of the flora genus of Ukraine, their prevalence and prospects for introduction into the culture, for further studies were selected raw materials of S. grandiflora, S. pratensis and S. verticillata. The aim. The aim of the study was to conduct a chromato-mass spectrometric study of the aboveground organs of S. grandiflora L., S. pratensis L. and S. verticillata L. to establish the prospects for the use of raw materials of these species in medical and pharmaceutical practice. Materials and methods. The objects of the study were leaves of S. officinalis, leaves, stems and flowers of S. grandiflora, S. pratensis and S. verticillata, which were harvested on the basis of the botanical garden of Ivan Franko National University of Lviv. The research of volatile substances in the objects of the research was carried out by the method of GC-MS on the basis of the Department of Natural Sciences for Foreign Students and Toxicological Chemistry of Zaporizhia State Medical University. Results. As a result of the study, 243 substances were found in the objects of the study, of which 149 were identified. 77 substances were found in the leaves of S. officinalis, 80, 26 and 63 substances in the leaves, stems and flowers of S. grandiflora, respectively, in the leaves , stems and flowers of S. pratensis – 28, 30 and 48 substances, respectively, in leaves, stems and flowers of S. verticillata – 39, 22 and 39 substances, respectively. Dominant compounds among substances of terpenoid nature are: cyclofenchene, camphene, 1,8-cineole, α-thujone, β-thujone, camphor borneol, caryophyllene, humulene, viridiflorol, sabinene, pyranone, β-pinene, phytol, kolavenol, β-copaen, loliolide, pseudolimonene and spatulenol. Among the dominant substances, 8 were detected for the first time in these species: cyclofenchene, viridiflorol, sabinene, pyranone, phytol, kolavenol, loliolide and pseudolimonene. Conclusions. The leaves of S. officinalis, leaves, stems and flowers of S. grandiflora, S. pratensis and S. verticillata of the flora of Ukraine were studied by chromato-mass spectrometric method. As a result of the study, 243 substances were identified, of which 149 were identified. Promising raw materials containing terpene compounds for S. grandiflora there are leaves, and for S. pratensis and S. verticillata – flowers, so they are promising agents for introduction into pharmaceutical practice
New S-substituted 4-alkyl-5-((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol derivatives have been designed, synthesized and studied their antimicrobial activity on 11 standard Gram-positive and Gram-negative microorganism strains. Their spectral and physicochemical parameters were established using modern comprehensive methods of analysis, including 1H NMR spectroscopy, GC-MS and elemental analysis.It has been found that compound 2a exhibits strong suppression of 5 test strains (MBC = 15.6 µg/mL). Compound 4a showed moderate inhibition of Salmonella pullorum, Escherichia coli O2, Salmonella enteritidis strains (MBC = 31.25 µg/mL) Compound 6a was sensitive toward ten tested bacteria at 31.25 µg/mL concentration.
The aim of the work. 1,2,4-triazole derivatives possess a wide range of pharmacological activity, so they are used for the development of drugs and active pharmaceutical ingredients. Due to the reactivity of 1,2,4-triazoles there are many options for their further structural modification on different reaction centers. Therefore, the aim of the work was to obtain new S-substituted derivatives of 1,2,4-triazole-3-thiols, study physicochemical parameters of the substances synthesized, evaluate the antimicrobial activity of new S-derivatives of the 4-R1-5-((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol series, and study some regularities of the “structure – biological activity” relationship for the synthesized compounds as well. Materials and methods. The subject of the study was new S-substituted 1,2,4-triazoles containing 2-oxopropan-1-yl and 2-aryl-2-oxoethan-1-yl substituents. The antimicrobial activity was studied by double serial dilutions on test cultures of Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 885-653). The results of the biological screening showed that at a concentration of 125 g/mL, all synthesized substances showed activity (MIC – in the range of 31.25 - 62.5 μg/mL, MBCK - in the range of 62.5–125 μg/mL) against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans. Variation of substituents on the sulfur atom did not lead to a significant change in antimicrobial and antifungal activities among derivatives of 4-R1-5-((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl) thio)methyl)-4H-1,2,4-triazole-3-thiols. Conclusions. Biological screening data indicate the prospects for the search for new antimicrobial substances among the abovementioned derivatives of 1,2,4-triazoles. The most active compounds were 1-((4-ethyl-5-((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazol-3-yl)thio)propan-2-one and 1-(4-methoxyphenyl)-2-(4-ethyl-5-(((3-(pyridin-4-yl)-1H)-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazol-3-yl)thio)ethanone, which showed the most pronounced antimicrobial activity against the Pseudomonas aeruginosa strain (MIC – 31.25 μg/mL, MBcK - 62.5 μg/mL)
About half of the drugs currently produced are chiral compounds, and about 90 % of these compounds are sold as racemates, consisting of an equimolar mixture of two enantiomers. Although they have the same chemical structure, most of the optical isomers of chiral substances show marked differences in biological activity. It is known that the presence of a single asymmetric atom has become almost an integral part of advanced drug design. The aim of this work was to determine the angle of rotation of the polarization plane of solutions of some S-derivatives of 4-R-5-((((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl))-4H-1,2,4-triazole-3-thiols and the establishment of regularities between the structure of the studied molecules and their optical activity. Materials and methods. The subject of the study was 2-[5-R1-4R2-1,2,4-triazole-3-ylthio]-1-aryletanols. The study of the angle of rotation of the plane of polarization of solutions of newly synthesized compounds was carried out using an Atago AP-300 polarimeter and the DFU 2.2.7 physical-chemical analysis method “Optical rotation”. Results. The results of the physical-chemical analysis were carried out that the studied compounds exhibit optical activity. The compound 1-((4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)-2-phenylethan-1-ol (+43° [deg∙g/cm3∙dm]). The only levorotatory substance was 1-(4-fluorophenyl)-2-((4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio))methyl)-4H-1,2,4-triazole-3-yl)thio)ethan-1-ol with specific rotation [α]D20 = -43° [deg∙g/cm3∙dm]. Conclusions. Studies had shown that 1-(4-fluorophenyl)-2-((4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl))thio)methyl)-4H-1,2,4-triazole-3-yl)thio)ethan-1-ol was able to rotate the light polarization plane to the left, which was evidence of the advantage of the S-enantiomer in the racemic mixture, and therefore this compound was considerable interest for further preclinical research. Also, all other analyzed compounds behave as optical isomers.
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