Promising fluconazole based zinc(II) and copper(II) coordination polymers against Chagas disease
José Aleixo de Azevedo-França1, Emile Barrias2, Chris Hebert Jesus Franco3
1Laboratório de Química Bioinorgânica e Catálise, Departamento de Química, ICE, Universidade Federal de Juiz de Fora, Juiz de Fora, MG. Brazil.
Abstract:
A series of new transition metal coordination polymers, [Zn(Ac)2(FLZ)2]n (1), [Zn(FLZ)2(Cl)2]n (2), {[Zn(FLZ)2](NO3)2}n (3), [Cu(FLZ)2(CH₃COO)4]n (4), {[Cu(FLZ)2Cl2]}n (5) and {[Cu(FLZ)2](NO3)2}n (6), were synthesized by the reaction of fluconazole (FLZ) with the respective zinc or copper salts under mild conditions. The molecular structure of these compounds was elucidated by several analytical and spectroscopy techniques such as elemental analyses, 1H and 13C{1H} nuclear magnetic resonance, electronic paramagnetic resonance, and infrared spectroscopy. Single-crystal X-ray diffraction confirmed the structure of the compounds 2, 4, 5 and 6 in solid state. The antichagasic activity of these compounds was evaluated against different forms of Trypanosoma cruzi. Compound 2 exhibited the highest activity against intracellular amastigotes. The ultrastructural changes in epimastigotes and intracellular amastigotes were investigated. These promising biological results demonstrated that the zinc or copper coordination polymers can form very active anti-parasitic compounds. The resulting compounds are more effective than the free azole drug and, consequently, great candidates for the treatment of Chagas disease.
