{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:23:27Z","timestamp":1790508207484,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":516,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Many compounds liberating NO (NO donors) have been used as therapeutic agents. Here we test two ruthenium nitrosyls, which release NO when activated by biological reducing agents, for their effects<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>against<jats:italic>Trypanasoma cruzi<\/jats:italic>, the agent responsible for the American trypanosomiasis (Chagas\u2019 disease).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Ruthenium NO donors were incubated with a partially drug\u2010resistant strain of<jats:italic>T. cruzi<\/jats:italic>and the anti\u2010proliferative and trypanocidal activities evaluated. In a mouse model of acute Chagas\u2019 disease, trypanocidal activity was evaluated by measuring parasitemia, survival rate of infected mice and elimination of amastigotes in myocardial tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic>, the observed anti\u2010proliferative and trypanocidal activities of trans\u2010[Ru(NO)(NH<jats:sub>3<\/jats:sub>)<jats:sub>4<\/jats:sub>isn](BF<jats:sub>4<\/jats:sub>)<jats:sub>3<\/jats:sub>and<jats:italic>trans<\/jats:italic>\u2010[Ru(NO)(NH<jats:sub>3<\/jats:sub>)<jats:sub>4<\/jats:sub>imN](BF<jats:sub>4<\/jats:sub>)<jats:sub>3<\/jats:sub>were due to NO liberated upon reduction of these nitrosyls. Ru(NO)isn had a lower IC<jats:sub>50epi<\/jats:sub>(67<jats:italic>\u03bc<\/jats:italic>M) than the NO donor, sodium nitroprusside (IC<jats:sub>50epi<\/jats:sub>=244<jats:italic>\u03bc<\/jats:italic>M) and Ru(NO)imN (IC<jats:sub>50try<\/jats:sub>=52<jats:italic>\u03bc<\/jats:italic>M) was more potent than gentian violet (IC<jats:sub>50try<\/jats:sub>=536<jats:italic>\u03bc<\/jats:italic>M), currently used in the treatment of blood. Both ruthenium nitrosyls eliminated,<jats:italic>in vivo<\/jats:italic>, extracellular as well as intracellular forms of<jats:italic>T. cruzi<\/jats:italic>in the bloodstream and myocardial tissue and allowed survival of up to 80% of infected mice at a dose (100 nmol kg<jats:sup>\u22121<\/jats:sup>day<jats:sup>\u22121<\/jats:sup>) much lower than the optimal dose for benznidazole (385<jats:italic>\u03bc<\/jats:italic>mol kg<jats:sup>\u22121<\/jats:sup>day<jats:sup>\u22121<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>Our data strongly suggest that NO liberated is responsible for the anti\u2010proliferative and trypanocidal activities of the ruthenium NO donors and that these compounds are promising leads for novel and effective anti\u2010parasitic drugs.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2007)<jats:bold>152<\/jats:bold>, 112\u2013121; doi:<jats:ext-link 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