Issue 32, 2015

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

Abstract

In search of prospective agents against infectious diseases, 1,1′-bis(diphenylphosphino)ferrocene pyridine-2-thiolato-1-oxide M(II) hexafluorophosphate compounds [M(mpo)(dppf)](PF6), where M = 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(diphenylphosphino)ferrocene molecules, both acting as bidentate ligands. Both compounds showed high cytotoxic activity on Trypanosoma cruzi 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 modelled T. cruzi NADH-fumarate reductase (TcFR) predicted that both be very good inhibitors of the enzyme. The effect of the compounds on the enzyme activity was experimentally confirmed using T. cruzi protein extracts. According to all obtained results, both [M(mpo)(dppf)](PF6) compounds could be considered prospective anti-trypanosomal agents that deserve further research.

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

Supplementary files

Article information

Article type
Paper
Submitted
06 Feb 2015
Accepted
05 Jul 2015
First published
07 Jul 2015

Dalton Trans., 2015,44, 14453-14464

Author version available

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

E. Rodríguez Arce, M. F. Mosquillo, L. Pérez-Díaz, G. A. Echeverría, O. E. Piro, A. Merlino, E. L. Coitiño, C. Maríngolo Ribeiro, C. Q. F. Leite, F. R. Pavan, L. Otero and D. Gambino, Dalton Trans., 2015, 44, 14453 DOI: 10.1039/C5DT00557D

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