Increased Lifespan of Leukemic Mice Treated with Drugs Related to (–)-Emetine

Abstract
The lifespan of mice bearing ascitic leukemia L1210 could be prolonged by treatment with (-)-emetine dihydrochloride. Optimal dosage schedules required emetine administration daily for 5 days (QD, day 1–5) or intermittently on every 4th day. (Q4D, day 1, 5, 9). Compounds related to (-)-emetine which are active in other biological systems, having the correct stereospecific structure at the C-1′ position in the molecule, a secondary amine structure at N-2′ and an ethyl-group substituent at C-3 were also effective in prolonging the survival time of L1210 leukemic mice. The effective compounds were (-)-cephaeline, (±)-2,3-dehydroemetine, (-)-2,3-dehydroemetine, (-)-tubulosine and (-)-O-methyltubulosine. In contrast, (-)-isoemetine and several derivatives of (±)-2,3-dehydroemetine, lacking the critical configuration at C-1′ or substitution at the N-2′ and C-3 positions in the molecule, were inactive in the mouse leukemia system, when administered according to the Q4D, day 1, 5, 9 schedule.