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

Abstract

2015): A new ruthenium cyclopentadienyl azole compound with activity on tumor cell lines and trypanosomatid parasites, Journal of Coordination Chemistry, 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(PPh 3 ) 2 (CTZ)](CF 3 SO 3 ) where Cp = cyclopentadienyl, CTZ = clotrimazole, was synthesized and characterized. The compound was evaluated in vitro on T. cruzi (Y strain), the infective form of T. brucei brucei 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 T. cruzi and on the tumor cell lines than the reference drugs (Nifurtimox and cisplatin, respectively). In addition, complexation of the bioactive CTZ to the {RuCp(PPh 3 )} 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 T. cruzi sterols of membrane and the interaction with DNA were studied. Although the tested complex does not affect DNA, it affects the T. cruzi biosynthetic pathway of conversion of squalene to squalene oxide. According to the results here reported, [RuCp(PPh 3 ) 2 (CTZ)][CF 3 SO 3 ] could be considered a prospective antiparasitic and/or antitumoral agent that deserves further evaluation.

Vanadium, Ruthenium and Copper Compounds: A New Class of Nonplatinum Metallodrugs with Anticancer Activity

“…Table 4 shows the structure-activity on several tumor cell lines of different ruthenium complexes. [114][115][116][117][118][119][120][121][122][123][124][125][126][127].…”

Half-Sandwich Ruthenium Arene Complexes Bearing Clinically Approved Drugs as Ligands: The Importance of Metal–Drug Synergism in Metallodrug Design

“…Coordination of cyclopentadienyl Ru moiety with CTZ drug and PPh 3 ligand resulted in complex 21f with dual antiparasitic and anticancer activities. It was found that 21f exhibited higher in vitro toxicity against T. cruzi than the well-known antiparasitic drug nifurtimox and better cytotoxicity than cisplatin in ovary, breast, and cervix cancer cells . The sterol biosynthesis inhibitory action in T. cruzi and DNA interaction of complex were examined to gain insight into the putative “dual” mechanism of antiparasitic activity.…”

“…It was found that 21f exhibited higher in vitro toxicity against T. cruzi than the well-known antiparasitic drug nifurtimox and better cytotoxicity than cisplatin in ovary, breast, and cervix cancer cells. 88 The sterol biosynthesis inhibitory action in T. cruzi and DNA interaction of complex were examined to gain insight into the putative "dual" mechanism of antiparasitic activity. The results showed that complex 21f had an impact on the biochemical mechanism of converting squalene to squalene oxide, despite the fact that it possessed weak interaction with DNA.…”

Multifunctional organometallic compounds for the treatment of Chagas disease: Re(i) tricarbonyl compounds with two different bioactive ligands

“…These promising results triggered the research of several groups around the world on metal compounds of these azole monodentate ligands. 13,14,18,39,40 Additionally, related Mn(I) tricarbonyls with some of the selected ligands have been successfully developed and tested on other trypanosomatid parasites and more recently on bacteria. 41,42 In summary, five new fac-[Re(CO) 3 (NN)(CTZ)](PF 6 ) compounds, with the NN shown in Fig.…”