| dc.description.abstract | Parasitic illnesses are major causes of human disease
and misery worldwide. Among them, both amebiasis and
Chagas disease, caused by the protozoan parasites, Entamoeba
histolytica and Trypanosoma cruzi, are responsible for
thousands of annual deaths. The lack of safe and effective
chemotherapy and/or the appearance of current drug resistance
make the development of novel pharmacological tools
for their treatment relevant. In this sense, within the framework
of the medicinal inorganic chemistry, metal-based drugs
appear to be a good alternative to find a pharmacological
answer to parasitic diseases. In this work, novel ruthenium
complexes [RuCl2(HL)(HPTA)2]Cl2 with HL = bioactive 5-
nitrofuryl containing thiosemicarbazones and PTA=
1,3,5-triaza-7-phosphaadamantane have been synthesized
and fully characterized. PTA was included as co-ligand
in order to modulate complexes aqueous solubility. In
fact, obtained complexes were water soluble. Their activity
against T. cruzi and E. histolytica was evaluated
in vitro. [RuCl2(HL4)(HPTA)2]Cl2 complex, with HL4=
N-phenyl-5-nitrofuryl-thiosemicarbazone, was the most
active compound against both parasites. In particular, it
showed an excellent activity against E. histolytica (half
maximal inhibitory concentration (IC50)=5.2 μM), even
higher than that of the reference drug metronidazole. In addition,
this complex turns out to be selective for E. histolytica
(selectivity index (SI) >38). The potential mechanism of antiparasitic
action of the obtained ruthenium complexes could
involve oxidative stress for both parasites. Additionally, complexes
could interact with DNA as second potential target by
an intercalative-like mode. Obtained results could be considered
a contribution in the search for metal compounds that
could be active against multiple parasites. | |
