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«Chemical structure-antitumor activity» bond correlation of new indolo[2,3-a]pyrrolo[3,4-c]carbazoles of N-glycosides classтезисы доклада
- Авторы: Kiseleva M.P., Borisova L.M., Golubeva I.S., Ektova L.V.
- Сборник: 4th Russian Conference on Medicinal Chemistry with international participants (MedChem Russia 10--14, 2019, Ekaterinburg, Russia)
- Серия: Abstract book (ISBN 978-5-7691-2521-8). Ekaterinburg: Ural Branch of the Russian Academy of Sciences
- Том: 448
- Тезисы
- Год издания: 2019
- Первая страница: 360
- Аннотация: Introduction. The research of «structure –activity» bond opens the best ways for the creation of new high selectivity and efficiency pharmaceutical products among the synthesized products of natural analogues or their structure chemical modification. The structure uniqueness and indolocarbazole N-glycosides biological properties stimulated the search and creation of active antitumor agents among their synthetic analogues and low-malecular derivatives.Objective. The goal of the work is to conduct a comparative study of 8 N-glycosides domestic derivatives of indolo[2,3-a]pyrrolo[3,4-c]carbazoles (LCS) with various modifications on aglycone and glycoside residue during the «structure-activity» bond analysis.Materials and methods. The research of the structure dependence of 8 indocarbasoles (LCS), synthesized in N.N. Blokhin Russian Cancer Research Center, and their antitumor activity was performed on transplantable mouse tumor models: lympoblastosis P388, lung Lewis epidermoid carcinoma (LLC) and B16 melanoma. The substances of conponds LCS were dissolved in dimethyl sulfoxide (DMSO) and diluted with saline to 10% of DMSO concentration. The compounds (LCS) were studies in doses of 25, 50 and 75 mg/kg with daily intraperitoneal administration for 5 days. The criteria for evaluation became the increase of life span of animals with P388 (ILS>25%) and the inhibition of solid LLC tumors and B16 (TGI>50%) growth.Results. On P388 all the compounds LCS demonstrated activity on ILS=31-115%. The aglycone-modified LCS compounds with the same glycosides showed effectiveness on solid models: xylose (TGI=52-84%) or arabinose (TGI=54-91%). The LCS compounds, similar in aglycone, but with different glycosides (galactose, xylose, ribose), had no effect on LLC, on B16 – TGI=70-84%.Conclusion. A comparative study of 8 N-glycosides derivatives of indolocarbazoles showed their effectiveness on P388 regardless of the modification changes in the aglycone structure. As for the LLC and B16 models, the antitumor LCS compounds activity depended on the structure of both, the aglycone and the glycoside residue. The obtained results can be proposed for analysis and synthesis of more active LCS compounds as new potential antitumor agents.
- Добавил в систему: Пугачева Ружена Борисовна