Aromatic amine N-oxide organometallic compounds: searching for prospective agents against tripanosoma Cruzi

ESTEBAN RODRÍGUEZ ARCE; M. FLORENCIA MOSQUILLO; LETICIA PÉREZ-DÍAZ; GUSTAVO A. ECHEVERRÍA; OSCAR E. PIRO; ALICIA MERLINO; E. LAURA COITIÑO; LUCÍA OTERO; DINORAH GAMBINO

Angra dos Reis

Congreso; 5th Latin American Symposium on Coordination and Organometallic Chemistry (5º SILQCOM); 2015

5th Latin American Symposium on Coordination and Organometallic Chemistry (5º SILQCOM)

AmericanTrypanosomiasis, 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, weresynthesized and fully characterized in the solid state and in solution. The compounds are isomorphous. M(II) ion is in anearly planar trapezoidal coordination bound to mpo and dppf molecules acting asbidentate ligands. Bothcompounds showed IC50 values in the nanomolar range on T. cruzi with good to excellentselectivity index values. The inclusion of the ferrocene moiety improved theselectivity towards the parasite when compared to the previously reported[M(mpo)2] complexes.1 Related to the probable mechanismof action of the complexes, molecular docking studies on modeled T. cruzi NADH-fumarate reductase (TcFR) predicted that both should be verygood inhibitors of the enzyme. The effect of the compounds on the enzymeactivity 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 agentsand leaders for furtherefforts in the design of better and more selective inhibitors against T. cruzi.