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

Author(s):Show less -

Rodriguez Arce, Esteban ^[1] ; Florencia Mosquillo, M. ^[2] ; Perez-Diaz, Leticia ^[2] ; Echeverria, Gustavo A. ^{[3, 4]} ; Piro, Oscar E. ^{[3, 4]} ; Merlino, Alicia ^[5] ; Laura Coitino, E. ^[5] ; Maringolo Ribeiro, Camila ^[6] ; Leite, Clarice Q. F. ^[6] ; Pavan, Fernando R. ^[6] ; Otero, Lucia ^[1] ; Gambino, Dinorah ^[1]

Affiliation

^[1] Univ Republica, Fac Quim, Dept Estrella Campos, Catedra Quim Inorgan, Montevideo 11800 - Uruguay

^[2] Univ Republica, Fac Ciencias, Lab Interacc Mol, Montevideo 11400 - Uruguay

^[3] Univ Nacl La Plata, Fac Ciencias Exactas, Dept Fis, RA-1900 La Plata, Buenos Aires - Argentina

^[4] Consejo Nacl Invest Cient & Tecn, Inst IFLP, CCT La Plata, RA-1900 La Plata, Buenos Aires - Argentina

^[5] Univ Republica, Fac Ciencias, Inst Quim Biol, Lab Quim Teor & Computac, Montevideo 11400 - Uruguay

^[6] UNESP, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP - Brazil

• Document type: Journal article
• Source: DALTON TRANSACTIONS; v. 44, n. 32, p. 14453-14464, 2015.
• Web of Science Citations: 18

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. (AU)

• FAPESP's process: 11/21232-1 - Evaluation of the involvement of eIF5A in the secretory pathway in Saccharomyces cerevisiae
• Grantee: Leonardo Biancolino Marino
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)