CHEMOTHERAPY OF EXPERIMENTAL TRYPANOSOMIASIS

I. Trypanocidal Activity of Certain Bis (2-Metkyl-4-Amino-6-Quinolyl) Amides and Ethers

¹ Sterling-Winthrop Research Institute, Rensselaer, New York

1. As a class the bis (2-methyl-4-amino-6-quinolyl) amides and ethers are trypanocidal; the variations of therapeutic activity against different strains and groups of trypanosomes are related to differences in chemical structure.

2. The compounds in which the bridge between the quinoline components is not a branched chain (i.e., the carbamide or urea derivative, the malonamide through the sebacamide, and the quinolyloxy alkanes) are the most active against the T. brucei group but are inactive against T. cruzi.

3. The branched chai n compounds (disubstituted malonamides) in which the branches are short alkyl chains (methyl-methyl through ethyl-propyl and ethylally!) are only weakly active against the T. brucei group but have activity against T. cruzi which increases directly with the length of the alkyl chains.

4. The peak of activity against T. cruzi is reached in those drugs in which one branch is either propyl or allyl and the other contains three or more carbons in either aliphatic or aromatic arrangement. These compounds are completely inactive against the T. brucei group.

5. The ratio of hydrogens in the two branches of the disubstituted malonamides seems to be as important for activity against T. cruzi as weight, configuration or saturation of the chains.

6. None of the amides or ethers studied has appreciable activity against T. congotense or L. donovani, although a close relative, the melamine "Congasin", is known to be active in the former infection.

7. Slight suppressive activity against T. lewisi and T. duttoni was shown by certain of the straight chain derivatives, and the latter organism was somewhat susceptible to prolonged treatment with some of the disubstituted malonamides which were ineffective against the former.

8. The compounds most active against the T. brucei group in preliminary screening and early evaluation tests in mice usually showed parallel activity in rabbit trypanosomiasis. The product most suitable for clinical use against T. cruzi was studied in relation to dosage and time of medication in both mice and dogs.

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