Metal complex derivatives of bis(pyrazol‑1‑yl)methane ligands: synthesis, characterization and anti‑Trypanosoma cruzi activity, 2018
In this work, the synthesis and characterization of seven complexes (1-7) was performed with Zn(I... more In this work, the synthesis and characterization of seven complexes (1-7) was performed with Zn(II), Cu(II), Co(II) and Ni(II) transition metals and ligands derived from bis(3,5-dimethylpyrazol-1-yl)methane (bdmpzm) and bis(3,5-dimethyl-4-nitro-1H-pyrazolyl)methane (L). The complexes were obtained in high yields, isolated as air-stable solids and characterized by physicochemical and spectroscopic methods. The structures of L and complex 1 were determined by single-crystal X-ray diffraction analysis. The complexes and their respective ligands were evaluated against epimastigotes of Trypanosoma cruzi strains. An increase in the activity of the complexes was observed compared to the free ligands. Greater activities were found for Co(II) complexes than for Cu(II), Ni(II) and Zn(II) complexes. Additionally, complexes 3 and 9 had little effect on erythrocytes, indicating that they are non-toxic. The results obtained in mitochondrial membrane potential analyses suggest a possible mechanism by which complex 3 has a trypanocidal effect through the induction of oxidative stress. The results could provide an interesting contribution to the further design of active complexes against T. cruzi.
Inhibition of C. albicans Dimorphic Switch by Cobalt(II) Complexes with Ligands Derived from Pyrazoles and Dinitrobenzoate: Synthesis, Characterization and Biological Activity, 2019
Seven cobalt(II) complexes of pyrazole derivatives and dinitrobenzoate ligands were synthesized a... more Seven cobalt(II) complexes of pyrazole derivatives and dinitrobenzoate ligands were synthesized and characterized. The single-crystal X-ray diffraction structure was determined for one of the ligands and one of the complexes. The analysis and spectral data showed that all the cobalt complexes had octahedral geometries, which was supported by DFT calculations. The complexes and their free ligands were evaluated against fungal strains of Candida albicans and emerging non-albicans species and epimastigotes of Trypanosoma cruzi. We obtained antifungal activity with a minimum inhibitory concentration (MIC) ranging from 31.3 to 250 µg mL −1. The complexes were more active against C. krusei, showing MIC values between 31.25 and 62.5 µg mL −1. In addition, some ligands (L1-L6) and complexes (5 and Co(OAc) 2 · 4H 2 O) significantly reduced the yeast to hypha transition of C. albicans at 500 µg mL −1 (inhibition ranging from 30 to 54%). Finally, the complexes and ligands did not present trypanocidal activity and were not toxic to Vero cells. Our results suggest that complexes of cobalt(II) with ligands derived from pyrazoles and dinitrobenzoate may be an attractive alternative for the treatment of diseases caused by fungi, especially because they target one of the most important virulence factors of C. albicans.
Metal complex derivatives of bis(pyrazol‑1‑yl)methane ligands: synthesis, characterization and anti‑Trypanosoma cruzi activity, 2018
In this work, the synthesis and characterization of seven complexes (1-7) was performed with Zn(I... more In this work, the synthesis and characterization of seven complexes (1-7) was performed with Zn(II), Cu(II), Co(II) and Ni(II) transition metals and ligands derived from bis(3,5-dimethylpyrazol-1-yl)methane (bdmpzm) and bis(3,5-dimethyl-4-nitro-1H-pyrazolyl)methane (L). The complexes were obtained in high yields, isolated as air-stable solids and characterized by physicochemical and spectroscopic methods. The structures of L and complex 1 were determined by single-crystal X-ray diffraction analysis. The complexes and their respective ligands were evaluated against epimastigotes of Trypanosoma cruzi strains. An increase in the activity of the complexes was observed compared to the free ligands. Greater activities were found for Co(II) complexes than for Cu(II), Ni(II) and Zn(II) complexes. Additionally, complexes 3 and 9 had little effect on erythrocytes, indicating that they are non-toxic. The results obtained in mitochondrial membrane potential analyses suggest a possible mechanism by which complex 3 has a trypanocidal effect through the induction of oxidative stress. The results could provide an interesting contribution to the further design of active complexes against T. cruzi.
Inhibition of C. albicans Dimorphic Switch by Cobalt(II) Complexes with Ligands Derived from Pyrazoles and Dinitrobenzoate: Synthesis, Characterization and Biological Activity, 2019
Seven cobalt(II) complexes of pyrazole derivatives and dinitrobenzoate ligands were synthesized a... more Seven cobalt(II) complexes of pyrazole derivatives and dinitrobenzoate ligands were synthesized and characterized. The single-crystal X-ray diffraction structure was determined for one of the ligands and one of the complexes. The analysis and spectral data showed that all the cobalt complexes had octahedral geometries, which was supported by DFT calculations. The complexes and their free ligands were evaluated against fungal strains of Candida albicans and emerging non-albicans species and epimastigotes of Trypanosoma cruzi. We obtained antifungal activity with a minimum inhibitory concentration (MIC) ranging from 31.3 to 250 µg mL −1. The complexes were more active against C. krusei, showing MIC values between 31.25 and 62.5 µg mL −1. In addition, some ligands (L1-L6) and complexes (5 and Co(OAc) 2 · 4H 2 O) significantly reduced the yeast to hypha transition of C. albicans at 500 µg mL −1 (inhibition ranging from 30 to 54%). Finally, the complexes and ligands did not present trypanocidal activity and were not toxic to Vero cells. Our results suggest that complexes of cobalt(II) with ligands derived from pyrazoles and dinitrobenzoate may be an attractive alternative for the treatment of diseases caused by fungi, especially because they target one of the most important virulence factors of C. albicans.
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Papers by Daniela Fonseca