CURE WITH CISPLATIN(II) OF MURINE MALARIA INFECTION AND IN-VITRO INHIBITION OF A CHLOROQUINE-RESISTANT PLASMODIUM-FALCIPARUM ISOLATE

Antiplasmodium properties of cisplatin [cis-platinum (II) diammine dic hloride], a neoplastic drug, have been assessed in in vivo and in vitr o model systems of malarial parasite. A well-tolerated dose of 6 mg/kg body weight of the compound cured the mice infected with Plasmodium b erghei and the amount of cisplatin required for in vitro inhibition (I C50) of a chloroquine-resistant Plasmodium falciparum isolate was smal ler than either chloroquine or quinine, The minimum inhibitory concent ration (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 schizont and ear ly ring stages were the least sensitive to the toxic effect of cisplat in. Multiple smaller doses were more effective in curing malaria in mi ce than a single large dose. In a few of the mice treated with a singl e intraperitoneal large dose of 6 mg/kg body weight, there was a delay in appearance of parasitemia but most of them recovered completely bu t slowly. This compound exerts its toxicity mainly by randomly damagin g and cross-linking DNA strands as shown by Southern hybridization wit h a synthetic oligonucleotide probe, which is a repeat sequence in the falciparum genome. The report clearly demonstrates the antimalarial p otentials of this compound and suggests a closer evaluation of this an d other related compounds, specially in combination with antimalarial drugs to probe their synergistic properties.