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Novel ruthenium(II) cyclopentadienyl thiosemicarbazone compounds with antiproliferative activity on pathogenic trypanosomatid parasites

Authordc.contributor.authorFernández, Mariana 
Authordc.contributor.authorRodríguez Arce, Esteban 
Authordc.contributor.authorSarniguet, Cynthia 
Authordc.contributor.authorMorais, Tânia S. 
Authordc.contributor.authorTomaz, Ana Isabel 
Authordc.contributor.authorOlea Azar, Claudio 
Authordc.contributor.authorFigueroa, Roberto 
Authordc.contributor.authorMaya Arango, Juan 
Authordc.contributor.authorMedeiros, Andrea 
Authordc.contributor.authorComini, Marcelo 
Authordc.contributor.authorGarcia, M. Helena 
Authordc.contributor.authorOtero, Lucía 
Authordc.contributor.authorGambino, Dinorah 
Cita de ítemdc.identifier.citationJournal of Inorganic Biochemistry 153 (2015) 306–314en_US
Identifierdc.identifier.otherDOI: 10.1016/j.jinorgbio.2015.06.018
General notedc.descriptionArtículo de publicación ISIen_US
Abstractdc.description.abstractSearching for new prospective antitrypanosomal agents, three novel Ru(II)-cyclopentadienyl compounds, [Ru(eta(5)-C5H5)(PPh3)L], with HL = bioactive 5-nitrofuryl containing thiosemicarbazones were synthesized and characterized in the solid state and in solution. The compounds were evaluated in vitro on the blood circulating trypomastigote form of Trypanosoma cruzi (Dm28c strain), the infective form of Trypanosoma brucei brucei (strain 427) and on J774 murine macrophages and human-derived EA.hy926 endothelial cells. The compounds were active against both parasites with IC50 values in the micromolar or submicromolar range. Interestingly, they are much more active on T. cruzi than previously developed Ru(II) classical and organometallic compounds with the same bioactive ligands. The new compounds showed moderate to very good selectivity towards the parasites in respect to mammalian cells. The global results point at [RuCp(PPh3)L2] (12 = N-methyl derivative of 5-nitrofuryl containing thiosemicarbazone and Cp = cyclopentadienyl) as the most promising compound for further developments (IC50 T. cruzi = 0.41 mu M; IC50 T. brucei brucei = 3.5 mu M). Moreover, this compound shows excellent selectivity towards T. cruzi (SI > 49) and good selectivity towards T. brucei brucei (SI > 6). In order to get insight into the mechanism of antiparasitic action, the intracellular free radical production capacity of the new compounds was assessed by ESR. DMPO (5,5-dimethyl-1-pirroline-N-oxide) spin adducts related to the bioreduction of the complexes and to redox cycling processes were characterized. In addition, DNA competitive binding studies with ethidium bromide by fluorescence measurements showed that the compounds interact with this biomolecule.en_US
Patrocinadordc.description.sponsorshipFONDECYT, Chile 1150175 1130189en_US
Type of licensedc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
Link to Licensedc.rights.uri*
Keywordsdc.subjectRuthenium cyclopentadienyl compoundsen_US
Keywordsdc.subjectTrypanosoma cruzien_US
Keywordsdc.subjectTrypanosoma bruceien_US
Títulodc.titleNovel ruthenium(II) cyclopentadienyl thiosemicarbazone compounds with antiproliferative activity on pathogenic trypanosomatid parasitesen_US
Document typedc.typeArtículo de revistaen_US

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Except where otherwise noted, this item's license is described as Atribución-NoComercial-SinDerivadas 3.0 Chile