Aromatic amine N-oxide organometallic compounds: searching for prospective agents against infectious diseases

E. RODRÍGUEZ ARCE; M. FLORENCIA MOSQUILLO; LETICIA PÉREZ-DÍAZ; GUSTAVO A. ECHEVERRÍA; OSCAR E. PIRO; ALICIA MERLINO; E. LAURA COITIÑO; CAMILA MARÍNGOLO RIBEIRO; CLARICE Q. F. LEITE; FERNANDO R. PAVAN; LUCÍA OTERO; DINORAH GAMBINO

DALTON TRANSACTIONS

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2015 vol. 44 p. 14453 - 14464

1477-9226

Searching for prospective agents against infectious diseases, 1,1´-bis (dipheny1phosphino) ferrocene pyridine-2-thiolato-1-oxide M(II) hexafluorophosphate compounds [M(mpo)(dppf)](PF6), where M(II) = palladium or platinum, were synthesized and fully characterized in the solid state and in solution using experimental and DFT computational techniques. The compounds are isomorphous and the M(II) transition metal ions are in a nearly planar trapezoidal cis-coordination bound to the pyridine-2-thiolato-1-oxide (mpo) and to the 1,1´-bis (dipheny1phosphino)ferrocene molecules, both acting as bidentate ligands. Both compounds showed high cytotoxic activity on Trypanosomacruzi and Mycobacterium tuberculosis (MTB) and acceptable selectivities towards MTB, but good to excellent selectivity index values as anti-T.cruzi compounds. The inclusion of the ferrocene moiety (dppf  ligand) improved the selectivity towards the parasite when compared to the previously reported [M(mpo)2] complexes. Related to the probable mechanism of action of the complexes, molecular docking studies on modeled T. cruzi NADH-fumaratereductase predicted that both should be very good inhibitors of the enzyme. According to all obtained results, both [M(mpo)(dppf)](PF6) compounds could be considered prospective anti-trypanosomal agents that deserve further research.