Cure with cisplatin (II) of murine malaria infection and in vitro inhibition of a chloroquine-resistant plasmodium falciparum isolate

Abstract

Antiplasmodium properties of cisplatin [cis-platinum (II) diam-mine dichloride], a neoplastic drug, have been assessed in in vivo and in vitro model systems of malarial parasite. A well-tolerated dose of 6 mg/kg body weight of the compound cured the mice infected with Plasmodium berghei and the amount of cisplatin required for in vitro inhibition (IC50) of a chloroquine-resistant Plasmodium falciparum isolate was smaller than either chloroquine or quinine. The minimum inhibitory concentration (MIC) needed to prevent the in vitro multiplication of asexual blood parasites was 30 ng/ml. Late ring and trophozoite stages of the erythrocytic cycle were the most susceptible, whereas schi-zont and early ring stages were the least sensitive to the toxic effect of cisplatin. Multiple smaller doses were more effective in curing malaria in mice than a single large dose. In a few of the mice treated with a single intraperitoneal large dose of 6 mg/kg body weight, there was a delay in appearance of parasitemia but most of them recovered completely but slowly. This compound exerts its toxicity mainly by randomly damaging and cross-linking DNA strands as shown by Southern hybridization with a synthetic oligonucleotide probe, which is a repeat sequence in the falciparum genome. The report clearly demonstrates the antimalarial potentials of this compound and suggests a closer evaluation of this and other related compounds, specially in combination with antimalarial drugs to probe their synergistic properties. © 1994, National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee. All rights reserved.