New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents

Abstract

In the search for new therapeutic tools against neglected diseases produced by trypanosomatid parasites, and particularly against African Trypanosomiasis, whose etiological agent is Trypanosoma brucei, organoruthenium compounds with bioactive nitrofuran containing thiosemicarbazones (L) as co-ligands were obtained. Four ruthenium(ii) complexes with the formula [Ru2(p-cymene)2(L)2]X2, where X = Cl or PF6, were synthesized and the crystal structures of two of them were solved by X-ray diffraction methods. Two of the complexes show significant in vitro growth inhibition activity against Trypanosoma brucei brucei and are highly selective towards trypanosomal cells with respect to mammalian cells (J774 murine macrophages). These promising results make the title organoruthenium compounds good lead candidates for further developments towards potential antitrypanosomal organometallic drugs.

Novel ruthenium(II) cyclopentadienyl thiosemicarbazone compounds with antiproliferative activity on pathogenic trypanosomatid parasites

“…Among the selected bioactive ligands a family of thiosemicarbazones containing the 5-nitrofuryl pharmacophore has been extensively studied by us [13]. We have rationally designed and developed more than sixty compounds of these ligands including palladium, platinum and ruthenium classical complexes as well as ruthenium η 6 -arene organometallic compounds and the effect of metal complexation and the presence of different co-ligands on the pharmacological profile of these bioactive ligands was evaluated [21][22][23][24][25][26][27][28][29][30][31][32][33].…”

5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms

“…The EC 50 were determined from dose-response assays at seven experimental concentrations (from 200 to 0.001 lM) of compounds tested in triplicate and essentially as described in Demoro et al 48 , except that 200 lL of a cell suspension at 6 Â 10 4 cells/ mL was added per well in a 96-well culture plate. The cytotoxicity was evaluated with a colorimetric assay (WST-1 reagent) that measures the absorbance at 450 nm of the formazan dye produced by metabolically active cells.…”

Thermodynamic Investigation of Interaction Between [(η 6-p-Cymene) RuII(Acetone-N 4-Phenylthiosemicarbazone)Cl]Cl Anticancer Drug and Human Serum Albumin: Spectroscopic and Electrochemical Studies

“…Recently, Ru(II)-arene complexes of thiosemicarbazone (TSC) with half-sandwich-type structure have emerged as novel strategies to develop promising lead Ru-based therapeutic drugs [1][2][3][4][5]. Some research has demonstrated the anticancer activity of Ru(II)-arene complexes of TSC anticancer drugs.…”