IFLP   13074
INSTITUTO DE FISICA LA PLATA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Aromatic amine N-oxide organometallic compounds: searching for prospective agents against tripanosoma Cruzi
Autor/es:
E. RODRÍGUEZ ARCE; M. F. MOSQUILLO; L. PÉREZ-DÍAZ; G. A. ECHEVERRÍA; O. E. PIRO; A. MERLINO; E. L. COITIÑO; L. OTERO ; D. GAMBINO
Lugar:
Angra dos Reis (RJ)
Reunión:
Simposio; 5th Latin American Symposium on Coordination and Organometallic Chemistry (5º SILQCOM); 2015
Institución organizadora:
Latin American Symposium on Coordination and Organometallic Chemistry (5º SILQCOM)
Resumen:
American Trypanosomiasis, caused by the protozoan parasite Trypanosoma cruzi, constitutes a major health concern in Latin America. Searching for prospective agents against T. cruzi, [M(mpo)(dppf)](PF6) compounds, where M = Pd(II) or Pt(II), dppf = 1,1'-bis (diphenylphosphino) ferrocene and mpo = pyridine-2-thiolato-1-oxide, were synthesized and fully characterized in the solid state and in solution. The compounds are isomorphous. M(II) ion is in a nearly planar trapezoidal coordination bound to mpo and dppf molecules acting as bidentate ligands. Both compounds showed IC50 values in the nanomolar range on T. cruzi with good to excellent selectivity index values. The inclusion of the ferrocene moiety improved the selectivity towards the parasite when compared to the previously reported [M(mpo)2] complexes.1 Related to the probable mechanism of action of the complexes, molecular docking studies on modeled T. cruzi NADH-fumarate reductase (TcFR) predicted that both should be very good inhibitors of the enzyme. The effect of the compounds on the enzyme activity was experimentally confirmed and studied in detail using T. cruzi protein extracts. According to all obtained results, both [M(mpo)(dppf)](PF6) compounds could be considered promising anti-trypanosomal agents and leaders for further efforts in the design of better and more selective inhibitors against T. cruzi.
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