title: Toward a novel metal-based chemotherapy against tropical diseases. 2. Synthesis and antimalarial activity in vitro and in vivo of new ruthenium- and rhodium-chloroquine complexes.
abstract: Chloroquine free base (CQ) reacts with [Rh(COD)Cl]2 (COD = 1,5-cyclooctadiene) and RuCl3.-3H2O/Zn to yield Rh(COD)(CQ)Cl (1) and [RuCl2(CQ)]2 (2), respectively. The two novel metal- CQ complexes, which were characterized mainly by 1D and 2D NMR spectroscopy, were tested against Plasmodium berghei. The in vitro activity of 1 was comparable to that of chloroquine diphosphate (CQDP), whereas 2 was about 5 times more active. In in vivo tests at equivalent concentrations of free CQ, CQDP reduced the parasitemia by 55%, while for complexes 1 and 2 the reduction reached 73% and 94%, respectively, without any sign of acute toxicity being observed up to 30 days after treatment. The Ru derivative 2 was further evaluated against two chloroquine-resistant strains of Plasmodium falciparum, and it was found to be 2-5 times more active than CQDP.
authors.affiliation: Transition Metal Chemistry, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela.
authors.forename: R A
authors.initials: RA
authors.lastname: Sánchez-Delgado
authors.forename: M
authors.initials: M
authors.lastname: Navarro
authors.forename: H
authors.initials: H
authors.lastname: Pérez
authors.forename: J A
authors.initials: JA
authors.lastname: Urbina
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002738:Chloroquine; D004351:Drug Resistance; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D009942:Organometallic Compounds; C098651:bis(ruthenium(chloroquine)dichloride); C098650:rhodium(1,5-cyclooctadiene)(chloroquine)chloride; D002738:Chloroquine