In vitro and in vivo activity of two Pt(IV) salts against leishmania donovani

The activities of 8 platinum drug complex salts were determined against Leishmania donovani promastigotes. The three most active salts were selected: PtIVBr6]H2 (pentamidine); PtIVBr6]H2 (stilbamidine), and PtIVCl6]H2 (2-piperazinyl(1) ethyl amine), which induced growth-inhibition rates of more than 50% at 24 h of treatment and at the maximum dosage tested. The cytotoxicity assays on the macrophage cell line J-774 showed high cytotoxicity for the salt PtIVBr6]H2 (stilbamidine) with a percentage of specific 51Cr release of 58.2% at 24 h of incubation and 100 microg/ml. Meanwhile, assays of the other compounds showed practically no cytotoxicity. The salt PtIVBr6]H2 (pentamidine) notably inhibited the incorporation of 3H-thymidine in the treated parasites. The ultrastructural alterations observed in the flagellates treated with the salts PtIVCl6]H2 (2-piperazinyl(1)ethyl amine) and PtIVBr6]H2 (pentamidine) suggest that both act preferentially at the nuclear level and at the kinetoplast-mitochondrion complex. Both compounds showed a high in vivo activity in parasitized Wistar rats.