Water-Soluble Ruthenium (II) Chiral Heteroleptic Complexes with Amoebicidal in Vitro and in Vivo Activity

Three
water-soluble Ru­(II) chiral heteroleptic coordination compounds
[Ru­(en)­(pdto)]­Cl2 (1), [Ru­(gly)­(pdto)]Cl (2), and [Ru­(acac)­(pdto)]Cl (3), where pdto =
2,2′-[1,2-ethanediylbis-(sulfanediyl-2,1-ethanediyl)]­dipyridine,
en = ethylendiamine, gly = glycinate, and acac = acetylacetonate,
have been synthezised and fully characterized. The crystal structures
of compounds 1–3 are described. The
IC50 values for compounds 1–3 are within nanomolar range (14, 12, and 6 nM, respectively). The
cytotoxicity for human peripheral blood lymphocytes is extremely low
(>100 μM). Selectivity indexes for Ru­(II) compounds are in
the
range 700–1300. Trophozoites exposed to Ru­(II) compounds die
through an apoptotic pathway triggered by ROS production. The orally
administration to infected mice induces a total elimination of the
parasite charge in mice faeces 1–2-fold faster than metronidazole.
Besides, all compounds inhibit the trophozoite proliferation in amoebic
liver abscess induced in hamster. All our results lead us to propose
these compounds as promising candidates as antiparasitic agents.