Cure With Cisplatin (Ii) of Murine Malaria Infection and in Vitro Inhibition of a Chloroquine-Resistant Plasmodium Falciparum Isolate

Abstract

SUMMARY:Antiplasmodium properties of cisplatin [cis-platinum (II) diammine 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 chloroquineresistant 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 schizont 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.241

In Vitro Antimalarial Activity of a Series of Cationic 2,2‘-Bipyridyl- and 1,10-Phenanthrolineplatinum(II) Benzoylthiourea Complexes

“…36 In addition, some of these compounds as well as other platinum complexes have been shown to exhibit antimalarial activity. 39,40 In the case of the compounds reported in this work however, we reasonably expect the chelated Pt(II) complexes to remain coordinatively intact under biological conditions. Since both ligands are bound in a bidentate mode to the Pt(II) ion, it is unlikely that they would undergo substitution reactions resulting in coordination to nucleic acids.…”

Platinum(II) and palladium(II) complexes with (N,N′) and (C,N,N′)− ligands derived from pyrazole as anticancer and antimalarial agents: Synthesis, characterization and in vitro activities

“…Cisplatin (Fig. 1) cured mice infected with Plasmodium berghei at a dose of 6 mg/kg body weight [76]. The Pd-cyclometallated derivative 5c was more efficient than Pt-protoporphyrin against P. falciparum (38 μM) [77].…”

Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells

“…Mislocalization of lysosomal and plasma membrane proteins has been noted in CDDP-resistant cells (17,21). In addition, disruption of lysosomes with bafilomycin A1 (17,22) and chlorquine (23) has been reported to alter CDDP cytotoxicity. Some of the genes whose products are involved in lysosome formation seem to influence cellular sensitivity to the cytotoxic effect of CDDP; these genes include the PI3 kinase (24), rho GTPases (25), annexins (26), and XIAP (27).…”