A new indolo[2,3-a]carbazole N-glycoside derivative LCS-1269 with antitumor activity on transplantable mice tumors

Background. The study of new representatives of indolo[2,3-a]carbazole N-glycosides with a biological activity broad spectrum remains a relevant direction in the highly effective antitumor drugs creation. Aim. To evaluate the efficacy of the lyophilized dosage form of a new derivative of indolocarbazole N-glycoside 6-picolinamido-12-(β-D-xylopyranosyl)indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione (LCS-1269-lyo) on transplantable mice colon adenocarcinoma (CAC) and on SW620 human colon cancer xenografts. Materials and methods. In studies on female Balb / c mice with subcutaneously (s.c.) transplanted CAC, a single intravenous (i.v.) administration of LCS-1269-lyo was used at doses of 80, 90, 100, 120 mg / kg and five-time administrataion daily at doses of 80 and 90 mg / kg. The LCS-1269-lyo study on SW620 effectiveness was carried out at doses of 60 and 90 mg / kg with five-time daily intraperitoneal (i.p.) administration to male Balb / c nude mice with subcutaneously transplanted SW620 xenografts. The antitumor effect was assessed by tumor growth inhibition and an increase in the lifespan of animals receiving LCS-1269-lyo, compared to the controls. Results. A dose-dependent reliable antitumor effect of LCS-1269-lyo was observed on CAС after a single exposure at doses of 80, 90, 100 and 120 mg / kg compared to the control group of mice. LCS-1269-lyo, when administered intravenously five times at doses of 80 and 90 mg / kg (total doses of 400 and 450 mg / kg), significantly inhibited CAC growth by 89–88 and 86–84 % ( p <0,05) over 30 days of observation and increased the life span of Balb / c mice by 36 and 54 %, respectively. The LCS-1269-lyo effectiveness in a total dose of 450 mg / kg on CAC has been confirmed by the activity of LCS-1269-lyo on SW620 xenografts in Balb / c nude mice with tumor growth inhibition 72,9–71,0 % ( p <0,05) during 8 days of observation. Conclusion. The results of the antitumor activity evaluation of LCS-1269 in a lyophilized dosage form on the model of CAC mice transplantable colon adenocarcinoma and on human colon cancer SW620 subcutaneous xenografts allow to continue preclinical studies of the drug.