A method has been defined for infecting primary mouse peritoneal macrophages with amastigotes of Leishmania donovani in vitro, and analysing the response of the infected macrophages to treatment with drugs. The growth of intracellular amastigotes was inhibited by all clinically used antileishmanial drugs. Toxic effects on macrophages were observed with some drugs. Other experimental antileishmanial compounds were active in this system. This test is proposed as an initial screening test for the discovery of novel antileishmanial compounds.
The aminoglycoside, aminosidine exhibited ED50S of between 1 and 5 microM against the amastigotes of Leishmania major and Leishmania tropica in mouse peritoneal macrophages whereas other strains causing New World cutaneous leishmaniasis such as Leishmania braziliensis were more refractory. Aminosidine was also active against all but one of the Leishmania donovani strains tested and when combined with sodium stibogluconate, the drug showed marked potentiation against the amastigotes of L. donovani in vitro and an additive effect in experimentally infected BALB/c mice.
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