Abstract

A series of organometallic drugs were tested in a photometric in vitro assay for trypanocidal activity against the three subspecies of the Trypanosoma brucei group. Trypanosoma b. rhodesiense, T. b. gambiense and T. b. brucei displayed a similar sensitivity pattern. The following IC50 values (drug concentration inhibiting decrease of extinction by 50%) could be determined: IrCl6 (IV)-Pentamidine (1.5 ng/ml), IrCl6(IV)-Ro15-0216 (10 micrograms/ml), PtBr6-Metamidium (30 micrograms/ml), PtBr6(IV)-Benznidazole (20 micrograms/ml), PtBr6(IV)-Ro15-0216 (50 micrograms/ml), cis-Pt(II)-Pentamidine (0.1 micrograms/ml), Rh(I)-COD-Pentamidine (5-10 ng/ml), Rh(I)-COD-Benznidazole (10 micrograms/ml), Rh(III)-Ethylxanthate (30 micrograms/ml) and Pt(II)-Pentamidine-cis-Pt(II)(Pentamidine)(Cl)2 (2 ng/ml). The four Pentamidine complexes were the most active compounds and showed activities comparable to that of Pentamidine (IC50: 0.5 to 1 ng/ml). Since the toxicity of the Ir- and Pt-Pentamidine complexes is ten to twenty fold lower (400 to 1000 mg/kg) than that of Pentamidine (50 mg/kg), the complexes might be candidates for investigation as safer trypanocidal drugs.