Coordination of nitro-thiosemicarbazones to ruthenium(II) as a strategy for anti-trypanosomal activity improvement

• Published in: European journal of medicinal chemistry Vol. 45; no. 7; pp. 2847 - 2853
• Main Authors: Rodrigues, Claudia, Batista, Alzir A., Ellena, Javier, Castellano, Eduardo E., Benítez, Diego, Cerecetto, Hugo, González, Mercedes, Teixeira, Letícia R., Beraldo, Heloisa
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 01.07.2010; Elsevier
• Subjects: Anti-trypanosomal activity; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Biological and medical sciences; Crystallography, X-Ray; Electrochemistry; Hemolysis - drug effects; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Organometallic Compounds - toxicity; Pharmacology. Drug treatments; Ruthenium - chemistry; Ruthenium(II) complexes; Spectrophotometry, Infrared; Thiosemicarbazones; Thiosemicarbazones - chemistry; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - growth & development; Anti-trypanosomal activity; Thiosemicarbazones; Ruthenium(II) complexes; Divalent metal Complexes; Nitro compound; Molecular structure; Toxicity; Cytotoxicity; Pyridine derivatives; Antiprotozoal agent; Ditertiary phosphine; Ruthenium II Complexes; Phenanthroline-ortho; Kinetoplastida; Hemolysis; Protozoa; Thiosemicarbazone; Organic ligand; Red blood cell; Bipyridines; Transition metal Complexes; X ray diffraction; In vitro; Biological activity; Trypanosoma cruzi; Parasiticide; Platinoid Complexes; Crystalline structure
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.03.005

Complexes [RuCl(H4NO 2Fo4M)(bipy)(dppb)]PF 6 ( 1), [RuCl(H4NO 2Fo4M)(Mebipy)(dppb)]PF 6 ( 2), [RuCl(H4NO 2Fo4M)(phen)(dppb)]PF 6 ( 3), [RuCl(H4NO 2Ac4M)(bipy)(dppb)]PF 6 ( 4), [RuCl(H4NO 2Ac4M)(Mebipy)(dppb)]PF 6 ( 5) and [RuCl(H4NO 2Ac4M)(phen)(dppb)]PF 6 ( 6) with N 4 -methyl-4-nitrobenzaldehyde thiosemicarbazone (H4NO 2Fo4M) and N 4 -methyl-4-nitroacetophenone thiosemicarbazone (H4NO 2Ac4M) were obtained from [RuCl 2(bipy)(dppb)], [RuCl 2(Mebipy)(dppb)], and [RuCl 2(phen)(dppb)], (dppb = 1,4- bis(diphenylphospine)butane; bipy = 2,2′-bipyridine; Mebipy = 4,4′-dimethyl-2,2′-bipyridine; phen = 1,10-phenanthroline). In all cases the thiosemicarbazone is attached to the metal center through the sulfur atom. Complexes ( 1– 6), together with the corresponding ligands and the Ru precursors were evaluated for their ability to in vitro suppress the growth of Trypanosoma cruzi. All complexes were more active than their corresponding ligands and precursors. Complexes ( 1– 3) and ( 5) revealed to be the most active among all studied compounds with ID 50 = 0.6–0.8 μM. In all cases the association of the thiosemicarbazone with ruthenium, dppb and bipyridine or phenanthroline in one same complex proved to be an excellent strategy for activity improvement. The association of a nitro-thiosemicarbazone with ruthenium(II), dppb = 1,4- bis(diphenylphospine)butane and bipyridine (bipy) or phenanthroline (phen) in one same complex proved to be an excellent strategy of anti- T. cruzi activity improvement. [Display omitted]