A new ruthenium cyclopentadienyl azole compound with activity on tumor cell lines and trypanosomatid parasites

<div><p>As part of our efforts to develop organometallic ruthenium compounds bearing activity on both trypanosomatid parasites and tumor cells, a new Ru(II)–cyclopentadienyl clotrimazole complex, [RuCp(PPh₃)₂(CTZ)](CF₃SO₃), where Cp = cyclopentadienyl, CTZ = clotrimazole, was synthesized and characterized. The compound was evaluated <i>in vitro</i> on <i>T. cruzi</i> (Y strain), the infective form of <i>T. brucei brucei</i> strain 427 (cell line 449), on three human tumor cell lines with different sensitivity to cisplatin (A2780, ovary; MCF7, breast; HeLa, cervix) and on J774 murine macrophages as mammalian cell model. The new compound is more cytotoxic on <i>T. cruzi</i> and on the tumor cell lines than the reference drugs (Nifurtimox and cisplatin, respectively). In addition, complexation of the bioactive CTZ to the {RuCp(PPh₃)} moiety leads to significant increase of the antiparasitic and antitumoral activity. To get insight into the potential “dual” mechanism of antiparasitic action emerging from the presence of Ru(II) and CTZ in a single molecule, the inhibitory effect of this new complex on the biosynthesis of <i>T. cruzi</i> sterols of membrane and the interaction with DNA were studied. Although the tested complex does not affect DNA, it affects the <i>T. cruzi</i> biosynthetic pathway of conversion of squalene to squalene oxide. According to the results reported here, [RuCp(PPh₃)₂(CTZ)][CF₃SO₃] could be considered a prospective antiparasitic and/or antitumoral agent that deserves further evaluation.</p>