In vitro activity of organometallic complexes of Ir, Pt and Rh on Trypanosoma b. gambiense, T. b. rhodesiense and T. b. brucei.
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.
Zinsstag
J
J
Swiss Tropical Institute, Basel.
Brun
R
R
Craciunescu
D G
DG
Parrondo Iglesias
E
E
D000818:Animals; D007495:Iridium; D009942:Organometallic Compounds / Q000494:pharmacology*; D010419:Pentamidine / Q000494:pharmacology; D010984:Platinum; D012238:Rhodium; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014347:Trypanosoma brucei gambiense / Q000187:drug effects*
D009942:Organometallic Compounds; D007495:Iridium; D010984:Platinum; D010419:Pentamidine; D012238:Rhodium