Introduction. Currently, more than 600 thousand people a year are affected by malignant tumors on the territory of the Russian Federation. Despite the large selection of antitumor drugs and the variety of mechanisms of their action, the effectiveness of existing drugs continues to be insufficient. The main disadvantages of most antitumor drugs are the emergence of tolerance to them of tumor cells, a limited range of action and high toxicity. In this regard, the creation of effective original domestic antitumor drugs still remains relevant. Among the numerous natural and synthetic heterocyclic compounds that exhibit antitumor activity, indolo[2,3-a]carbazole derivatives that can initiate various pathways of tumor cell death are of increasing interest. The main targets for their action are topoisomerases and protein kinases, which play an important role in the processes of replication, transcription, repair or recombination of deoxyribonucleic acid (DNA). Due to this, in addition to antitumor activity, this group of compounds shows antibacterial, аntiprotozoal and immunomodulatory activity, which makes them a very promising class of candidates for the creation of new drugs.Text. The purpose of this review is to discuss instrumental methods for qualitative and quantitative analysis of indolo[2,3-a]carbazole derivatives used in the world's leading pharmacopoeias. These methods can be used both in pharmacokinetic studies, and in the standardization of these compounds, in the form of pharmaceutical substances, or as part of drug forms.Conclusion. To further introduce a new group of antitumor drugs based on indole[2,3-a]carbazole derivatives into medical practice, a deep and thorough study of their physical and chemical properties is necessary. Justification and development of analysis methods allow us to develop methods applicable to pharmacokinetic studies, as well as to create regulatory documents for quality control and standardization of indolo[2,3-a] carbazole derivatives as pharmaceutical substances. A study of the literature that describes methods for analyzing indolo[2,3-a]carbazole derivatives indicates that spectrometric (infrared and ultraviolet spectrometry) and chromatographic (thin-layer chromatography and high-performance liquid chromatography) methods are most often used to determine the authenticity and quantitative analysis of these compounds.
Bryansk State Academician I.G. Petrovski University Through the analysis of the essential features of a transaction as a special ideal phenomenon for establishing a legal connection, the phenomenon of will and expression of will in an invalid transaction is revealed. It is concluded that the basis of the transaction, unlike other legal actions, is the freedom of will of the persons committing it. In view of this, if the will is erroneous, the entire transaction is invalidated and turns into an even more unique phenomenon – an invalid transaction, the essence of which is to enable the parties to correct the error. In conclusion, specific changes to the norms of the Civil Code of the Russian Federation are proposed.
Indolocarbazole glycosidic derivative LCS-1269 with significant antiproliferative activity has been synthesized in N.N. Blokhin National Medical Research Center of Oncology. To control the quality of the substance, the chromatographic method of the assay was created and validated. The technique was carried out in a gradient mode using mobile phases consist of acetonitrile, trifluoroacetic acid and purified water. The specificity of the method was shown by checking of test solutions and the special solvent chromatograms. The method linearity was confirmed, and the parameters of linear dependence have been estimated, and the relationship was described by the equation: y = 49.23× – 35.51 with correlation coefficient 0.9998. The method’s precision was determined as the repeatability with a relative error of the mean 1.49% and was 2.433 ± 0.036. Was shown, that the results obtained in the intermediate precision estimation were not burdened with a systematic error. The detection limit and quantitation limit were calculated based on the linear relationship data as 3.15 μg/mL and 9.57 μg/mL, respectively. Sensitive HPLC method for LCS-1269 assay in substance has been developed and validated.
Introduction. Indolocarbazole derivatives are of increasing scientific interest for practical oncology. A number of N-glycosides, indolo[2,3-a] carbazole under the laboratory code LCS, were synthesized in the laboratory of chemical synthesis of the National Medical Center of Oncology named after N.N. Blokhin. Currently, one of the most promising compounds in this class is LCS-1208, a representative of the arabinoside class of indolo [2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione. According to the mechanism of biological action, LCS-1208 is a protein kinase C inhibitor and is of great interest for the treatment of malignant neoplasms.Aim. chemical and pharmaceutical standardization of the pharmaceutical substance LCS-1208.Materials and methods. Laboratory samples of pharmaceutical substance LCS-1208. Methods of investigation: gravimetry, spectrophotometry, polarimetry, high-performance liquid chromatography (HPLC), high-resolution nuclear magnetic resonance (NMR) spectroscopy and infrared (IR) spectroscopy.Results and discussion. The quality assessment of LCS-1208 was carried out according to the indicators adopted in the XIV edition of the State Pharmacopoeia of the Russian Federation for quality control of pharmaceutical substances. LCS-1208 - orange amorphous powder, odorless; soluble in dimethylsulfoxide (DMSO) and dimethylformamide (DMF); very slightly soluble in 95 % ethyl alcohol and practically insoluble in water. The authenticity of the substance is confirmed by NMR and IR spectra, as well as electronic absorption spectra. The values of the specific optical rotation of LCS-1208 (1 % solution in DMF) are placed in the range from +58° to +61°. All the studied samples of the substance were free of inorganic impurities, sulphate ash, heavy metals and contained no more than 1.0 % water, determined by the K. Fischer titration method. The content of possible related impurities in the substance LCS-1208 and the content of the main active substance were determined by HPLC. The studied laboratory series of the pharmaceutical substance LCS-1208 contained no more than 1.0 % of any single and no more than 3 % of the total unidentified impurities. The content of the main active substance was more than 97 %.Conclusion. As a result of the work carried out, quality criteria and parameters were selected and methods for their determination were developed, which allow to adequately assess the quality and standardness of the pharmaceutical substance LCS-1208.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.