Comparative Amoebacidal Activity of Some Compounds Related to Emetine. †

Summary and conclusions

1. Members of 2 different series of compounds were tested against cultures of E. histolytica grown with E. coli. 2. E-2 proved the more effective of the 2 quaternary emetine derivatives, exhibiting an amoebacidal endpoint of 500 μg per ml; this was 10 times as effective as E-1. 3. Of the series of phenylalkylamides of phen-ylalkylaminoisovaleric acids, V-3 and V-1 proved approximately 10 times more effective than the corresponding methoxy-substituted moieties. V-3 was the most amoebacidal of all the above compounds, with an amoebacidal endpoint of 200 μg per ml, while the endpoint for V-1 was 500 μg per ml. 4. The amoebacidal activity of the compounds was shown to be independent of effects upon the associated bacterial flora, as measured both by surviving bacterial populations and oxidation-reduction potentials of the cultures. This activity was definitely influenced, however, by the pH during tests, more alkaline conditions being correlated with greater effectiveness. 5. Parallel tests with aureomycin, included to reveal effects of a distinctly antibacterial agent, supported the conclusion that, unlike aureomycin, the present series of compounds had acted directly against the amoebae.

Some concluding observations on structure activity relationship. Quaternization of both nitrogens in the emetine molecule (E-1) yielded weak amoebacidal action. E-2, with only one quaternized nitrogen, proved a considerably stronger amoebacidal agent. It might be concluded that quaternization of the nitrogen atoms in the emetine molecule decreases amoebacidal activity, the number of quaternized nitrogen atoms being inversely proportional to amoebacidal action. Correlation of the pharmacologic studies on the quaternary emetine derivatives(14) with the amoebacidal tests indicates that, although quaternization of both nitrogens produced a compound lacking the cumulative and cardio-toxic effects of the original alkaloid, this derivative exhibited a strong curare-like action but only weak amoebacidal properties.