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.

A series of 11 triazenes (X-C6H4N=NNRCH3) was characterized for toxicity in mice (LD50). The quantitative structure-activity relationship (QSAR) obtained for toxicity was compared with the QSAR for antitumor activity. The close correspondence of the two QSAR leaves essentially no means for the synthesis of more potent, less toxic triazenes.

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