Antiparasitic activities of novel ruthenium/lapachol complexes

The present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2 '-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4 '-methylbipyridine (Me-bipy) and 4,4 '-methoxybipyridine (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy-3-(3-33 methyl-2-buthenyl)-1,4-naphthoquinone) as bidentate ligand. The [Ru(Lap)(PPh3)(2)(bipy)]PF6 (1), [Ru(Lap)(PPh3)(2)(Me-bipy)]PF6 (2), [Ru(Lap)(PPh3)(2)(MeO-bipy)]PF6 (3) and[Ru(Lap)(PPh3)(2)(Phen)]PF6 (4) complexes, PPh3 = triphenylphospine, were synthesized from the reactions of cis-[RuCl2(PPh3)(2)(X-bipy)] or cis-[RuCl2(PPh3)(2)(phen)], with lapachol. The [RuCl2(Lap)(dppb)] (5) [dppb = 1,4-bis(diphenylphosphine)butane] was synthesized from the mer-[RuCl3(dppb)(H2O)] complex. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV-vis spectroscopy, P-31{H-1) and H-1 NMR, and cyclic voltammetry. The Ru(III) complex, [RuCl2(Lap)(dppb)], was also characterized by the EPR technique. The structure of the complexes [Ru(Lap)(PPh3)(2)(bipy)]PF6 and [RuCl2(LaP)(dPpb)] was elucidated by X-ray diffraction. The evaluation of the antiparasitic activities of the complexes against-Leishmania amazonensis and Plasmodium falciparum demonstrated that lapachol-ruthenium complexes are more potent than the free lapachol. The [RuCl2(Lap)(dppb)] complex is the most potent and selective antiparasitic compound among the five new ruthenium complexes studied in this work, exhibiting an activity comparable to the reference drugs. (C) 2014 Elsevier Inc. All rigts reserved.