Structural and spectroscopic characterization of epiisopiloturine-metal complexes, and anthelmintic activity vs. S. mansoni

Abstract

Epiisopiloturine (EPI), extracted from leaves of Pilocarpus microphyllus, a plant originally from the Amazon and Savanna regions in Brazil, was described as a potential drug against Schistosomiasis, a neglected severe disease. Herein, EPI was complexed with copper(II) or zinc(II) salts and the isolated species, [Cu(epi)4](ClO4)2 (1) and [Zn(epi)2Cl2] (2), were structurally and spectroscopically characterized. By using X-ray diffraction, the crystal structures of both metal complexes were determined, indicating a square pyramidal geometry for copper for 1 and a tetrahedral environment around zinc for 2. EPR spectra of 1 show a typical tetragonal environment around the central metal ion with some tetrahedral distortion, both in the solid state and in frozen acetonitrile solution, in accordance with crystallographic data. For 2, NMR spectra have bands consistent with a tetrahedral species in solid state or in DMSO-d6 solution. These spectroscopic characterization data were further supported by Density Functional Theory calculations, showing that these metal complexes are also stable in solution. Those metal complexes were tested against adult worms of Schistosoma mansoni, in comparison to the free alkaloid as anthelmintic agent. Coordination with copper(II) improved the alkaloid schistosomicidal properties, while binding to zinc(II) decreased its activity.