Drug development & registration最新文献

{"title":"Scientific, Methodological and Organizational Approaches to Conducting Pre-clinical and Expert studies of Substances with Psychoactive Properties","authors":"T. Malkova, P. S. Mashchenko, A. I. Andreev, D. Apushkin, E. V. Vikhareva","doi":"10.33380/2305-2066-2023-12-4(1)-1614","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1614","url":null,"abstract":"Introduction. Studying the psychoactive properties of substances is an important task for regulating their circulation. It is relevant both for new psychoactive substances (NPS) that are in illegal circulation and for drugs entering the pharmaceutical market. In this regard, the issue of creating specialized analytical centers for conducting complex chemical and pharmacological studies does not lose its relevance.Aim. The purpose of the work is to develop scientific, methodological and organizational approaches to conducting comprehensive studies of psychoactive substances based on generalizing the work experience of employees of the Regional Test Center (RTC) \"Pharmatest\" of the Perm State Pharmaceutical Academy, both in the study of new psychoactive substances, withdrawn from illegal circulation, as part of expert studies on behalf of law enforcement agencies, and as part of preclinical studies of new medicines.Materials and methods. When performing the work, experimental and statistical data for 2010–2023 were used. on the study of NPS on the basis of the RTC \"Pharmatest\" in order to determine the possibility of classifying them as analogues of drugs of abuse, materials on the study of new drugs for the possible presence of psychoactive properties and affinity for certain receptors, approaches to conducting individual stages of expert examinations were assessed and described research, chemical and biological methods used.Results and discussion. The stages of research into new psychoactive substances and the methodology for conducting tests on each of them, as well as the necessary equipment and approaches to interpreting the results obtained, have been determined and scientifically substantiated. The need to create analytical centers to conduct comprehensive expert studies of narcotic substances and preclinical studies of drugs is shown.Conclusion. The developed methodological principles and organizational measures for conducting a comprehensive study of new psychoactive substances are important both for suppressing illegal drug trafficking in order to implement the State anti-drug policy, and for the development of domestic pharmaceuticals, designed to ensure the use of effective and safe medicines in medical practice.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139157185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective Activity of Pine cones Extract","authors":"D. K. Gulyaev, S. S. Zykova, V. D. Belonogova, D. O. Semakin, N. Buzmakova","doi":"10.33380/2305-2066-2023-12-4(1)-1613","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1613","url":null,"abstract":"Introduction. Fatty hepatosis is a widespread metabolic disease. There is an annual increase in cases of detection of fatty hepatosis both in Russia and around the world. An urgent task is to search for new medicines for the treatment and prevention of the development of fatty hepatosis.Aim. Investigation of the composition of procyanidins and the biological activity of pine cones extract on a model of fatty hepatosis in vivo.Materials and methods. To obtain the extract, cones of pine harvested on the territory of the Perm Region in December were used. The extract was obtained by processing raw materials with hot water. The component composition of procyanidins in the extract was determined using ultra-efficient liquid chromatography with a mass selective detector. Hepatoprotective activity was studied on a model of fatty hepatosis induced by the introduction of carbon tetrachloride in vivo on white mongrel rats. Silymarin was used as a reference for comparison.Results and discussion. As a result of chromatographic examination, the following procyanidins were identified in a dry aqueous extract of pine cones – B2, B3, C1, C2, D1. As a result of hepatoprotective activity, it was found that no changes were detected in the control (intact) group during the pathohistological examination of the liver. Index (degree) of steatosis: 0. In the experimental group, whose animals were injected with carbon tetrachloride without subsequent treatment, it was found that about 50 % of hepatocytes of the histological section were in a state of macro- and microvesicular fatty dystrophy. The steatosis index is 2. In the group of animals injected with carbon tetrachloride and treated with Karsil®, normalsized hepatocytes with single fatty microvesicles in the cytoplasm. The steatosis index is 0. In the group of animals injected with carbon tetrachloride and treated with pine cones extract, hepatocytes of normal size with an euchromic nucleus, in the central parts in a state of macro- and microvesicular fatty dystrophy (about 20-25 % of all hepatocytes of the histological section). The steatosis index is 1.Conclusion. The extract of pine cones contributes to a moderate decrease in the prevalence of protein, small-focal small-droplet fatty dystrophy of hepatocytes. To increase hepatoprotective activity, it is necessary to investigate the effect of the extract at a dose of 30 mg/kg and above.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"41 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139155893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of Analytical Methods for Quality Control of Gel for Dentin Remineralization","authors":"A. L. Golovanenko, E. S. Berezina, I. V. Alekseeva, O. A. Oleshko","doi":"10.33380/2305-2066-2023-12-4(1)-1656","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1656","url":null,"abstract":"Introduction. As a result of a complex of scientific and experimental studies carried out at the Department of Pharmaceutical Technology of the State Pharmacy of Pharmaceuticals, a gel was developed for remineralization of dentin in order to carry out drug treatment of medium and deep caries. In the developed gel, along with the remineralizing effect, an antibacterial effect was achieved, which is necessary in the treatment of dentin caries due to the introduction of chlorhexidine bigluconate (CHB). The proposed composition simultaneously contains the main remineralizing ions – calcium, phosphate and fluoride in a free active state. Due to this, a significant increase in their penetration into the dentin is ensured. During the preparation of regulatory documentation for the gel for the treatment of dentine caries, validation of methods designed to control the quality of active substances was carried out.Aim. Validation of methods for testing the authenticity and quantification of active substances in the gel for dentine remineralization.Materials and methods. To achieve this goal, active pharmaceutical substances of pharmacopoeial quality are used. When developing test methods, pharmacopoeial and non-pharmacopoeial reactions to reacting cations and anions were used. For the quantitative determination of the chloride compound, the complexometric method, the back titration method is used, for potassium phosphate, the disubstituted acidimetric method, for sodium fluoride, the photoelectrocolorimetric method, for chlorhexidine bigluconate, the lauryl sulfate method. The objects of study were five serial samples of gels.Results and discussion. As a result of the studies, methods of testing for authenticity were developed, it was found that the proposed methods are characterized by a negative analytical signal on model mixtures free of the analyte and placebo, and a positive analytical signal on model mixtures of various compositions containing the analyte. The validation characteristics of methods for the quantitative determination of active substances in the gel were studied, positive results were obtained, the proposed methods can be used for inclusion in the regulatory documentation for the developed gel.Conclusion. When evaluating the validation characteristics of the proposed methods, it was found that the methods of testing for authenticity and quantitative determination of active substances in the gel are specific, the methods of quantitative determination are characterized by accuracy and repeatability, a linear dependence in the analytical region of ±20 % of the declared amount of active substances, which allows them to be used for reliable assessment of the quality of the developed gel.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"23 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Creation of a Scientific System for Analyzing the Scientific Activities of a University as a Source of Innovation in the Production of Medicines","authors":"E. V. Sokolova, P. Guryanov, A. G. Salnikova, T. Malkova","doi":"10.33380/2305-2066-2023-12-4(1)-1618","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1618","url":null,"abstract":"Introduction. The creation of new medicines and their introduction into production depends, in particular, on the organization of scientific research in pharmaceutical universities. The ability to fully utilize all the material, financial and human resources available to a university determines the possibility of effectively generating pharmaceutical innovations. This, in turn, is possible if there are methods of scientific analysis of the process of scientific activity of a university.Aim. Creation of methods for scientific analysis of the process of scientific activity of a university, allowing, on the basis of regularly collected information about the scientific activity of departments, to identify areas for improving the organization of scientific research.Materials and methods. The study used logical, analytical-synthetic research methods, modeling, and the method of expert assessments. The scientific reports of the Perm State Pharmaceutical Academy (PSFA) departments for 2019 were studied.Results and discussion. A model of the functioning of the scientific activities of a university has been developed using the example of PSFA, reflecting the degree of interaction of individual departments with each other. Original methods for assessing the effectiveness of individual departments were developed based on the ratio of material, financial, and human resources invested in the work of the departments, and the scientific and practical output obtained as a result of scientific activities.Conclusion. The created model for organizing the scientific activities of the university made it possible to identify departments as “generators” and “successors of scientific research”, as well as the phenomenon of imbalance or lack of interaction between departments. Original methods for assessing human resources and scientific output of the department have been created. To evaluate the work of the department, a rule was formulated for the balance between the resources invested in the work of the department and the scientific result obtained, as well as the balance between the scientific output itself, expressed in scientific publications, and the practical output, expressed in received patents, grants and implementation acts.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"5 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139155457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of New Derivatives of 2,4-dioxobutanoic Acid Salts in Behavioral Studies of Laboratory Animals","authors":"A. I. Krasnova, V. D. Polezhaeva, N. A. Pulina","doi":"10.33380/2305-2066-2023-12-4(1)-1591","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1591","url":null,"abstract":"Introduction. Correction of pathological anxiety is currently an important task of modern pharmacology, since anxiety disorders are among the most common mental illnesses. Taking into account the trend of a constant increase in the incidence of anxiety and depressive disorders (ADD) in the world, the urgency of searching for various tools for studying this group of diseases and creating safe, highly effective drugs for the pharmacotherapy of ADD is growing.Aim. The study of new derivatives of salts of 2,4-dioxobutanoic acids containing fragments of benzimidazole and pyrimidine cycles on behavioral reactions of animals.Materials and methods. The salts of 4-methoxyphenyl-4-oxobut-2-enoic acid with heterocyclic amines synthesized by us were used as objects of research. Behavioral reactions of animals to the introduction of the studied compounds were evaluated using a number of tests: \"open field\", light/dark box\", \"extrapolation escape task\", \"forced swim\".Results and discussion. The results of the experiments made it possible to identify a potentially active compound 1b, which showed an improvement in a number of indicators of motor activity of animals and an anti-anxiety effect. In addition, with the introduction of substance 1b, there is a manifestation of antidepressant activity in an acute stress situation.Conclusion. The effect of compounds 1a, 1b obtained for the first time on the behavioral reactions of animals was studied. The \"structure-activity\" analysis was carried out with the establishment of the priority of further targeted synthesis of salts of 2,4-dioxobutane acid derivatives containing a fragment of 2-aminopyrimidine. A compound with a neuropsychotropic activity profile has been identified, which is recommended for further in-depth study.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"14 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of Technological Parameters and Pharmacological Activity of the Gel with Strawberry (Fragaria ananassa) Leaves with Dry Extract","authors":"O. V. Yaborоva, I. V. Alekseeva, V. D. Belonogova, O. A. Oleshko","doi":"10.33380/2305-2066-2023-12-4(1)-1657","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1657","url":null,"abstract":"Introduction. Interest in herbal preparations is increasing every year, as the variety of chemical composition and pharmacological action of plants makes it possible to discover and create drugs whose therapeutic effect is due to a complex of biologically active substances. It is important for the effective treatment of diseases to have a properly selected dosage form, which provides both ease of use and targeted use of the action of the pharmacologically active drug contained in it. Therefore, obtaining and introducing new plant extracts into medical practice can become promising in the field of creating soft dosage forms. Strawberry garden leaf extract dry (strawberry extract) is one of the potential substances for obtaining effective and safe medicines. According to the results of earlier studies conducted by the staff of the Perm State Pharmaceutical Academy of the Ministry of Health of the Russian Federation, a high anti-inflammatory activity of strawberry extract was proved, comparable to the activity of the synthetic drug Indomethacin. Studies of the chronic toxicity of the extract, allergenic, immunotoxic properties and reproductive toxicity in the framework of preclinical studies have shown the safety of the obtained extract and the possibility of using the substance for further development of medicines based on it. In this regard, the study of technological parameters and pharmacological activity of a soft dosage form based on strawberry extract is of practical interest for improving the drug supply of the population and expanding the range of medicines based on plant extracts with anti-inflammatory and antimicrobial effects.Aim. Development of a soft dosage form based on strawberry leaves of dry extract and study of its pharmacological activity.Materials and methods. For the study, gels with an active substance – strawberry leaves with dry extract (JSC \"Biohimmash\", Russia, shelf life – 2 years), the main components – sodium carboxymethylcellulose C75 (TU 2231-002-50277563-2000, LLC \"Base chemical products \"Yugreactive\", Russia, 151118, term storage 3 years), methylcellulose 35 (TU 2231-107-57684455-2003, JSC \"UZPH\", Russia, 221218, shelf life 3 years), sodium alginate (TU 15-02-544-83, LLC \"Base сhemical products \"Yugreactive\", Russia, 151018, shelf life 3 years), glycerol (FS.2.2.0006.15, JSC \"Kupavnareaktiv\", Russia, 082018, shelf life 3 years), purified water (FS FS.2.2.0020.18), obtained at the reverse osmosis unit UVOI-\"MF\" 1812S6 (JSC \"NPK MEDIAN FILTER\", Russia). Вiopharmaceutical and technological methods were used in the course of the research. Antimicrobial activity was determined according to the OFS.1.2.4.0010.15 by diffusion into agar. Anti-inflammatory activity was studied on a model of acute inflammatory edema caused by subplantar injection of 0.1 ml of 1 % aqueous solution of carrageenan into the hind paw of a rat. The obtained data were processed with the calculation of the Student's t-test for independent samples. Th","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"23 34","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Antioxidant Properties and Cytotoxic Activity of 1,3-dioxolane Derivatives Imidazole","authors":"S. S. Zykova, M. V. Shustov, V. Talismanov","doi":"10.33380/2305-2066-2023-12-4(1)-1655","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1655","url":null,"abstract":"Introduction. Modern chemotherapy widely considers the role of antioxidant and pro-oxidant methods in the treatment of oncologic pathologies. The use of agents that cause an increase of ROS is a relevant way to destroy tumors. At the same time, there is evidence of the ability of some antioxidants to lead to the cancer cells apoptosis through the generation of free radical forms of oxygen due to disruption of cellular homeostasis. The combination of the «Ecolum» biosensor using technique, antiradical activity data, and information about the cytotoxicity of compounds used in the study allows us to consistently conduct low-cost screening of as antioxidant, as antiradical activities and potentially reduce the required number of expensive cytotoxicity determinations using tumor cells.Aim. The main target of our work is the evaluation of antioxidant and cytotoxic activities of 1,3-dioxolane derivatives of imidazole using antioxidant, antiradical and cytotoxicity tests in vitro.Materials and methods. To carry out this study, 1,3-dioxolane derivatives of imidazole were obtained. The antiradical tests was performed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Antioxidant properties were assessed within the Ecolum biosensor in the state of oxidative stress. Cytotoxic activity was assessed in GIST-T1 cell culture using the MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide).Results and discussion. Data from studies of the antioxidant activity of substances using the «Ecolum» biosensor showed varying degrees of damage to the biosensor in the absence of antioxidant action. The antiradical potential, initially used to reveal a possible mechanism of antioxidant action, actually demonstrated a possible mechanism of toxic action of substance 2c due to its antiradical effect comparable to the standard (Trolox), but the substance has the highest cytotoxicity. However, the properties of substance 2a shows that the direct correlation discussed earlier is not found in all cases.Conclusion. The asessment of the antioxidant properties and cytotoxic activity of 1,3-dioxolane derivatives of imidazole demonstrated the relevance of further searching for connections between the results of substances binding with the Ecolum biosensor under conditions of oxidative stress, their antiradical potential and cytotoxic properties. This combination of tests will potentially reduce the cost of screening through the use of an available biosensor, establish a possible mechanism of action aimed at redox balance, and confirm previously obtained data through the use of tumor cell culture.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"20 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139157429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of the Method for Spectrofluorimetric Determination of Aluminum Impurities in Substances","authors":"E. V. Vishnyakov, A. A. Tolstikova, J. E. Generalova, A. K. Kaldybaeva, I. I. Terninko","doi":"10.33380/2305-2066-2024-13-1-1530","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-1-1530","url":null,"abstract":"Introduction. Evaluation of the content of impurities is the most important step in confirming the safety and efficacy in the quality control of the medicinal product. Aluminum, being an acceptable impurity in a number of pharmaceutical substances, can adversely affect the human body, as a result of which its content is normalized. The admixture of aluminum in the State Pharmacopoeia of the Russian Federation XV is determined by the spectrofluorimetric method using the ligand – 8-hydroxyquinoline in chloroform. In the present work, it is proposed to replace 8-hydroxyquinoline with the more accessible rutin, which also forms fluorescent complexes with metals. This approach involves the exclusion of the stage of extraction of the aluminum complex into chloroform from sample preparation, which improves the accuracy of the technique, and the replacement of chloroform has a positive effect on safety.Aim. To create an alternative approach for the spectrofluorimetric determination of aluminum impurities using rutin and \"potassium chloride\" as an active pharmaceutical ingredient.Materials and methods. The following substances and reagents were used as research materials: CRS of aluminum ion 1 mg/ml (LLC \"EKROSHIM\", Russia), CRS of iron ion (II) 1 mg/ml (LLC \"EKROSHIM\", Russia), CRS of zinc ion 1 mg/ml (LLC \"EKROSHIM\", Russia), CRS of lead-ion 1 mg/ml (LLC \"EKROSHIM\", Russia), CRS nickel-ion 1 mg/ml (LLC \"EKROSHIM\", Russia), CRS copper-ion 1 mg/ml (LLC \"EKROSHIM\", Russia), chromium (III) cation standard 1 mg/ml (imp., Sigma-Aldrich, USA) rutin (imp., Sichuan Guangsong Pharmaceutical Co., Ltd., China), ammonium acetic acid (imp., Molekula GmbH, Germany), glacial acetic acid (chemically pure, JSC \"Base No. 1 Himreaktivov\", Russia), potassium chloride (pharmaceutical substance, LLC \"MZHR\", Russia). The spectrofluorimetric study was carried out on an FL 6500 instrument (PerkinElmer Inc., USA). The aluminum impurity content was also evaluated using an Optima 8000 inductively coupled plasma atomic emission spectrometer (ICP AES) (PerkinElmer Inc., USA) and a Multi-Element Solution standard sample (PerkinElmer Inc., USA).Results and discussion. The approach given in the article eliminates the use of 8-hydroxyquinoline in chloroform and replaces it with rutin in 70 % ethyl alcohol. The aluminum-rutin complex has an excitation wavelength at 445 nm and an emission wavelength at 565 nm. The proposed method was tested on the substance \"Potassium chloride\" to assess the indicator \"Aluminum\", the content of which should not exceed 0.0001 %. Method validation was carried out according to three parameters \"Specificity\", \"Linearity\" and \"Limit of detection\". Comparison of the data obtained was carried out using atomic emission spectroscopy, during which the relevance of the technique was proved.Conclusion. An ergonomic approach has been developed for the spectrofluorimetric determination of aluminum impurities using rutin with approbation on the substance \"Potassium chlor","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"47 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139158634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the «Structure – analgesic activity» Relationship Using Molecular Docking for Cyclooxygenases 1 and 2 in the Series 5-N-arylaminocarbonyl-6-(get)aryl-4-methyl-1,2,3,6-tetrahydropyrimidine-2-thiones","authors":"N. Buzmakova, K. V. Аndryukov, T. M. Zamaraeva, I. P. Rudakova, K. V. Podchezertseva, A. S. Goman, E. V. Avdeeva, N. V. Slepova, N. V. Dozmorova","doi":"10.33380/2305-2066-2023-12-4(1)-1600","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1600","url":null,"abstract":"Introduction. Molecular modeling methods are very popular in the scientific community at the present time. The value of the pharmacological action depends on the affinity of the substance to the biological target. Molecular docking makes it possible to assess the degree of affinity of the studied compound with the active center of the molecular target. The enzyme cyclooxygenase (COX) plays a key role in the cascade of synthesis of proinflammatory cytokines and, as a consequence, in pain.Aim. To identify the dependence \"structure – analgesic activity\" using the method of molecular docking for cyclooxygenase type 1 and type 2 in the series of 5-N-arylaminocarbonyl-6-(get)aryl-4-methyl-1,2,3,6-tetrahydropyrimidine-2-thions.Materials and methods. 19 compounds 5-N-arylaminocarbonyl-6-(get)aryl-4-methyl-1,2,3,6-tetrahydropyrimidine-2-thions are objects of research The study of the interaction of tetrahydropyridine derivatives with COX 1 and 2 was carried out by the method of molecular docking by the AutoDock 4 program using scoring functions.Results and discussion. Molecular docking of 5-N-arylaminocarbonyl-6-(get)aryl-4-methyl-1,2,3,6-tetrahydropyrimidine-2-thions (I–XIX) with COX 1 and 2 is described. Quantitative studies of the \"structure – analgesic activity\" in the studied series of compounds of the dependence of experimental values of analgesic activity (ААex.) on scoring functions (BeCOX1, KiCOX1, BeCOX2, KiCOX2) and physico-chemical descriptors (log Ppred., рКаpred., рКvpred.) were performed. By checking on an independent sample of 5 compounds, equation No. 3 (ААpred. 3 = 32,6215 – 4,4894 × Becox1 + 0,0066 × Kicox1 + 3,6032 × log Ppred. (R = 0,854, F = 9,01, S = 7,73, Q2LOO = 0,53) was found, with a high value of the correlation coefficient of the predicted values ААex. with experimental values (Rpred. = 0,878) and a minimum forecast error (Spred. = 6,74).Conclusion. The \"structure-activity\" models for predicting analgesic activity in a series of 5-N-arylaminocarbonyl-6-(get)aryl-4-methyl-1,2,3,6-tetrahydropyrimidine-2-thions are obtained. The result of the prediction of biological activity is confirmed by the values of the correlation coefficient (R) obtained when testing models on independent samples.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"50 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139164241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Quality Control of Calcium Chelidonate Substance with Osteogenic Activity","authors":"E. Avdeeva, N. M. Igidov, V. L. Gein, S. Krivoshchekov, I. Khlusov, M. V. Belousov, N. V. Dozmorova, V. Luzhanin","doi":"10.33380/2305-2066-2023-12-4(1)-1678","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1678","url":null,"abstract":"Introduction. Osteogenic agents are used for pathologies associated with impaired bone formation, complications of bone fractures, the use of implants and endoprostheses, and tumor lesions of bone tissue. High osteogenic activity in vivo on the model of experimental osteomyelitis, in vitro and in situ on mesenchymal stem cells was revealed for calcium chelidonate, which is a promising substance for the production of osteogenic drugs.Aim. Development of a method for obtaining the calcium chelidonate substance by chemical synthesis and methods of its standardization.Materials and methods. The synthesis of chelidonic acid was carried out on the basis of diethyloxalate; calcium chelidonate – using synthesized chelidonic acid and anhydrous calcium chloride. The structure of the substances was confirmed by optical spectral methods, mass spectrometry, elemental and X-ray structural analysis. The quantitative content was assessed using a liquid chromatograph. Statistical processing of the results of quantitative measurements was carried out in the STATISTICA 8,0 program.Results and discussion. As a result of the synthesis, chelidonic acid (4-oxo-4H-piran-2,6-dicarboxylic acid) was obtained, which is colorless or cream-tinged crystals. The structure of the resulting compound is confirmed by spectral characteristics and elemental analysis data. A method for obtaining the calcium chelidonate substance has been worked out, while the yield of the target product was 100 ± 5 %. By X-ray structural analysis, it was found that the synthesized compound is calcium chelidonate trihydrate [Ca(ChA)(H2O)3]n with M.M. (C7H8O9Ca) 276,15. Methods for establishing authenticity, purity and quantification of the substance have been developed. The amount of impurities in the resulting substance did not exceed 0.1 %, and the content of the main component ranged from 99,2 ± 0,20 to 100,4 ± 0,35 %.Conclusion. Due to the limited resource reserves and the complexity of the process of extracting chelidonic acid from plant raw materials, a method for the chemical synthesis of calcium chelidonate substance with osteogenic activity is proposed. The obtained results provide prospects for further research in the direction of the development and introduction of synthetic calcium chelidonate as a new osteogenic drug, provided that the specific biological activity is comparable to the natural analogue.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"16 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139164502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}