title: 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.
authors.affiliation: Cátedra de Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, Gral. Flores 2124, 11800 Montevideo, Uruguay. dgambino@fq.edu.uy luotero@fq.edu.uy.
authors.forename: Esteban
authors.initials: E
authors.lastname: Rodríguez Arce
authors.forename: M Florencia
authors.initials: MF
authors.lastname: Mosquillo
authors.forename: Leticia
authors.initials: L
authors.lastname: Pérez-Díaz
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Echeverría
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Piro
authors.forename: Alicia
authors.initials: A
authors.lastname: Merlino
authors.forename: E Laura
authors.initials: EL
authors.lastname: Coitiño
authors.forename: Camila
authors.initials: C
authors.lastname: Maríngolo Ribeiro
authors.forename: Clarice Q F
authors.initials: CQ
authors.lastname: Leite
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pavan
authors.forename: Lucía
authors.initials: L
authors.lastname: Otero
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
mesh_terms: D000588:Amines / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000737:chemistry; D008024:Ligands; D000075163:Metallocenes; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010087:Oxides / Q000737:chemistry*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism; D010165:Palladium / Q000737:chemistry; D010720:Phosphines / Q000737:chemistry; D010984:Platinum / Q000737:chemistry; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000588:Amines; D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D005296:Ferrous Compounds; D008024:Ligands; D000075163:Metallocenes; D009942:Organometallic Compounds; D010087:Oxides; D010720:Phosphines; D010984:Platinum; D010165:Palladium; D044925:Oxidoreductases Acting on CH-CH Group Donors; C020155:fumarate reductase (NADH); C519379:1,1'-bis(diphenylphosphino)ferrocene