Место издания:Ural Branch of the Russian Academy of Sciences (Ekaterinburg) Ekaterinburg
Первая страница:360
Последняя страница:360
Аннотация:Introduction. The research of «structure –activity» bond opens the best ways forthe creation of new high selectivity and efficiency pharmaceutical products among thesynthesized products of natural analogues or their structure chemical modification. Thestructure uniqueness and indolocarbazole N-glycosides biological properties stimulated thesearch and creation of active antitumor agents among their synthetic analogues and lowmalecular derivatives.Objective. The goal of the work is to conduct a comparative study of 8 N-glycosidesdomestic derivatives of indolo[2,3-a]pyrrolo[3,4-c]carbazoles (LCS) with variousmodifications on aglycone and glycoside residue during the «structure-activity» bondanalysis.Materials and methods. The research of the structure dependence of 8 indocarbasoles(LCS), synthesized in N.N. Blokhin Russian Cancer Research Center, and their antitumoractivity was performed on transplantable mouse tumor models: lympoblastosis P388,lung Lewis epidermoid carcinoma (LLC) and B16 melanoma. The substances of conpondsLCS were dissolved in dimethyl sulfoxide (DMSO) and diluted with saline to 10% of DMSOconcentration. The compounds (LCS) were studies in doses of 25, 50 and 75 mg/kg with dailyintraperitoneal administration for 5 days. The criteria for evaluation became the increase oflife 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%. Theaglycone-modified LCS compounds with the same glycosides showed effectiveness on solidmodels: xylose (TGI=52-84%) or arabinose (TGI=54-91%). The LCS compounds, similar inaglycone, but with different glycosides (galactose, xylose, ribose), had no effect on LLC, onB16 – TGI=70-84%.Conclusion. A comparative study of 8 N-glycosides derivatives of indolocarbazolesshowed their effectiveness on P388 regardless of the modification changes in the aglyconestructure. As for the LLC and B16 models, the antitumor LCS compounds activity dependedon the structure of both, the aglycone and the glycoside residue. The obtained results canbe proposed for analysis and synthesis of more active LCS compounds as new potentialantitumor agents.