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Activity of 8-Aminoquinolines against Leishmania Tropica within Human Macrophages in Vitro^*

Antileishmanial activity of 8-aminoquinolines with substitutions on the quinoline ring or on the 8-amino side-chain was assessed in the Leishmania tropica-infected human macrophage in vitro model of leishmaniasis. The 4-methyl-5,6-dimethoxy compounds were more active than 6-methoxy compounds, which were approximately as active as 4-methyl-6-methoxy compounds. Certain 6-hydroxy compounds were the most active drugs tested. The precise composition of substituents on the 8-amino side-chain had little effect on activity. These investigations identify WR 226292 (a 4-methyl-5,6-dimethoxy compound) and WR 6881 and WR 49577 (6-hydroxy compounds) as the most active 8-aminoquinolines in this in vitro model. The 6-hydroxy compounds also can be considered to be the 6-demethyl derivatives of 6-methoxy-8-aminoquinolines. This study therefore indicates that 6-demethyl-8-aminoquinolines may be generally more active in vitro than the parent 6-methoxy structures against macrophage-contained Leishmania.

Accepted for publication July 26, 1982.

^* Address reprint requests to: MAJ Berman, Department of Parasitology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, D.C. 20012.

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