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Master's Dissertation
DOI
https://doi.org/10.11606/D.75.2020.tde-19052020-155723
Document
Author
Full name
Victor Maia Miranda
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2020
Supervisor
Committee
Deflon, Victor Marcelo (President)
Poelhsitz, Gustavo von
Rocha, Fillipe Vieira
Title in Portuguese
Obtenção e avaliação da atividade tripanocida de novos complexos quadrático-planares de metais divalentes do grupo 10
Keywords in Portuguese
doença de Chagas
níquel (II)
paládio (II)
platina (II)
tiossemicarbazona
Abstract in Portuguese

Neste trabalho, três novos complexos de níquel (II), paládio (II) e platina (II) contendo os ligantes 5-hidroxi-3-metil-5-fenilpirazolina-1-(4-metil-3-tiosemicarbazona) (H2bmt) e trifenilfosfina (PPh3) foram sintetizados, com rendimentos satisfatórios, e caracterizados. As caracterizações dos complexos [Ni(bmt)PPh3] (1), [Pd(bmt)PPh3] (2) e [Pt(bmt)PPh3] (3) foram feitas por meio de análise elementar, espectroscopia vibracional na região do infravermelho, espectroscopia de absorção na região do UV-Visível, RMN – 1H, RMN – 13C{1H}, RMN – 31P{1H}, espectrometria de massas de alta resolução e difração de raios X por monocristal. As técnicas de caracterização confirmam que os complexos possuem as estruturas propostas, apresentando, portanto, geometria quadrática-planar, em que os centros metálicos estão coordenados pelos sítios doadores O, Nimina e S do ligante H2bmt, formando dois anéis quelatos, e pelo átomo de fósfofo do ligante PPh3. Os ensaios de atividade antiparasitária in vitro contra a forma tripomastigota do protozoário Trypanosoma cruzi (T. cruzi) mostraram que o complexo 1 possui ação tripanocida e que a atividade biológica da tiossemicarbazona H2bmt é potencializada quando complexada com o NiII. A complexação com o PdII e a PtII não provocou uma melhora na atividade tripanocida da H2bmt. Os ensaios de citotoxicidade dos complexos frente a macrófagos indicaram que os compostos possuem seletividade pela forma tripomastigota do T. cruzi. Ao se analisar os resultados dos ensaios biológicos, é possível verificar que a reatividade do centro metálico, possivelmente associada com a geometria molecular que o complexo apresenta, é um fator que modula a atividade tripanocida dos compostos descritos neste trabalho.  

Title in English
Development and evaluation of trypanocidal activity of novel Group 10 divalent metals square-planar complexes
Keywords in English
Chagas disease
nickel (II)
palladium (II)
platinum (II)
thiosemicarbazone
Abstract in English

In this work, three novel nickel (II), palladium (II), and platinum (II) complexes containing the ligands 5-hydroxi-3-methyl-5-phenylpyrazoline-1-(4-methyl-3-thiosemicarbazone) (H2bmt) and triphenylphosphine (PPh3) were synthesized with satisfactory yields and characterized. The complexes [Ni(bmt)PPh3] (1), [Pd(bmt)PPh3] (2), and [Pt(bmt)PPh3] (3) were characterized by elemental analysis, vibrational spectroscopy in the infrared region, absorption spectroscopy in the UV-Visible region, 1H – NMR, 13C{1H} – NMR, 31P{1H} – NMR, high resolution mass spectrometry, and single crystal X ray diffraction. The characterization techniques confirmed the complexes have square-planar geometry, in which the metallic centers are coordinated by the O, Nimine, and S donor sites of ligand H2bmt, forming two chelate rings, and by the phosphorus atom of ligand PPh3. The in vitro biological assays with the trypomastigote form of the protozoa Trypanosoma cruzi (T. cruzi) showed that complex 1 exhibits trypanocidal activity and the complexation of H2bmt with NiII potentializes the thiosemicarbazone biological activity. The complexation with PdII and PtII resulted in no trypanocidal activity improvement for H2bmt. The cytotoxicity assays with macrophages indicated that the compounds are selective towards the trypomastigote form of T. cruzi. By analyzing the biological results, it is observed that the metallic center reactivity, possibly associated with the molecular geometry of the complex, modulates the trypanocidal activity of the compounds described in this work. 

 
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Publishing Date
2020-05-26
 
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