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.
Departamento de Biología Aplicada, Facultad de Ciencias Experimentales, Universidad de Almería, Madrid, España.
C M
CM
Mesa-Valle
M N
MN
Rodriguez-Cabezas
V
V
Moraleda-Lindez
D
D
Craciunescu
M
M
Sanchez-Moreno
A
A
Osuna
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002460:Cell Line; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000648:ultrastructure; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D010419:Pentamidine / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D017671:Platinum Compounds / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013266:Stilbamidines / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity
D000981:Antiprotozoal Agents; D017671:Platinum Compounds; D013266:Stilbamidines; D010419:Pentamidine; C042560:stilbamidine