PRECLINICAL STUDY OF INDOLOCARBAZOLES N-GLYCOSIDES DERIVATIVE LCS-1208 ANTITUMOR ACTIVITY. REPORT I

Abstract

This article presents the results of preclinical study of antitumor activity of indolo[2,3-a]carbazoles N-glycosides derivative (LCS-1208) in pharmaceutical dosage form for intravenous administration - lyophilisate for injection. LCS-1208 high antitumor efficiency has been shown by different regimens of administration on tumors of diverse histogenesis: LCS-1208 exhibited increase of life span (ILS) 76% on lympoblastosis P-388 and ILS 76 % and 33 % recovery of Fisher lympadenosis L5178Y by 25 mg/kg daily intravenous administration during 5 days. Whereas LCS-1208 demonstrated high antitumor efficiency on solid tumors by 150 mg/kg single intravenous dosing: on LLC - tumor growth inhibition (TGI) 95% - 81% during 9 days and on RShM-5 (TGI 74% - 56% during 9 days). LCS-1208 appeared statistically significant TGI 51 % and 47 % on 3rd and 7th days after 150 mg/kg single intravenous dosing on established tumor. Comparative study of LCS-1208 substance and dosage form by intraperitoneal injection has shown that decrease of therapeutic dose to 110 mg/kg, which doesn’t induce death of animals, resulted only in dosage form antitumor effect (TGI 74-75 % during 8 days after the end of treatment).