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Master's Dissertation
DOI
https://doi.org/10.11606/D.75.2014.tde-28082014-162915
Document
Author
Full name
Murilo César Carroccia
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2014
Supervisor
Committee
Deflon, Victor Marcelo (President)
Ferreira, Ana Maria da Costa
Mauro, Antonio Eduardo
Title in Portuguese
Complexos de oxovanádio(V) com ligantes hidrazonas bioativos: síntese, caracterização estrutural e estudo da potencial atividade tripanocida
Keywords in Portuguese
atividade tripanocida
caracterização estrutural
hidrazonas
oxovanádio(V)
Abstract in Portuguese
A doença de Chagas, também chamada de tripanossomíase americana é a terceira doença parasítica mais presente no mundo, perdendo apenas para malária e esquistossomose. As terapias existentes atualmente para essa tripanossomíase são insatisfatórias e pouca atenção tem sido dada para o desenvolvimento de novos fármacos. Os medicamentos utilizados atualmente apresentam boa atividade apenas na fase inicial da doença e geram efeitos colaterais severos nos pacientes.
As hidrazonas representam uma classe de compostos imínicos de grande versatilidade estrutural e importante atividade biológica em diversos níveis, sendo observados resultados de atividade tripanocida interessantes de hidrazonas coordenadas a rutênio. Por outro lado, complexos com oxovanádio coordenado a derivados de quinoxalinas apresentam melhores atividades do que os ligantes na forma livre e que complexos formados por essas quinoxalinas com outros metais.
Esse trabalho buscou unir as propriedades biológicas das hidrazonas e vanádio de forma a obter complexos com boa atividade tripanocida. Foram sintetizados dois ligantes hidrazonas derivados da 2-tiofenofenohidrazida, e através dos mesmos foram desenvolvidos dez novos complexos de oxovanádio (V). Os produtos foram caracterizados por ponto de fusão, análise elementar, espectroscopia na região do infravermelho e do UV-Vis., ressonância magnética nuclear (RMN 1H) e difração de raios X em monocristal, sendo obtidos três classes de complexos. Duas classe são formadas por complexos com ligantes mistos, na forma [VO(L)(OR)] com R=metil, etil, n-propil e L=hidrazona, e na forma [VO(L)(mal)] com L=hidrazona e mal= pirona maltol. Outra classe obtida é formada por binucleares de oxovanádio na forma [(VOL)2(μ-O)] com L=hidrazona e os centros de vanádio ligados por uma ponte μ-oxo. As estruturas obtidas para os complexos mistos com os alcóxidos e para os dímeros apresentam geometria piramidal quadrática distorcida, enquanto que os complexos mistos com maltol apresentam geométrica octaédrica distorcida.
Ensaios in vitro contra cepas de T. cruzi mostraram resultados interessantes (SI iguais ou maiores que 10) para que continue a exploração dos tipos de complexos formados e novos ensaios biológicos devem ser realizados para verificar o mecanismo de ação e a atividade in vivo desses compostos, com intuito de obter um novo fármaco antichagásico baseado em vanádio no futuro.
Title in English
Oxovanadium(V) complexes with bioactive hydrazones ligands: synthesis, structural characterization and study of the potencial trypanocidal activity
Keywords in English
hydrazones
oxovanadium(V)
structural characterization
trypanocidal activity
Abstract in English
Chagas disease, also called American trypanosomiasis is the third most present parasitic disease in the world. The existing therapies for this trypanosomiasis are unsatisfactory and a little attention has been given to the development of new drugs. The drugs currently used exhibit good activity only in the early phase of the disease and generate severe side effects in patients.
Hydrazones represent a class of iminic compounds with good structural variability and important biological activity at various levels, and interesting results of trypanocidal activity are observed for hydrazones coordinated to ruthenium. On the other hand, complexes with oxovanadium coordinated to quinoxaline derivatives have better activities than the free ligands and complexes with other metals coordinated to that quinoxalines.
This study aimed to unite the biological properties of hydrazones and vanadium to obtain complexes with good trypanocidal activity. Two hydrazones ligands derived from 2- tiofenofenohidrazida were synthesized, and through that ligands, ten new complexes of oxovanadium (V) were developed. The products were characterized by melting point, elemental analysis, infrared and UV - Vis. spectroscopies, nuclear magnetic resonance (1H NMR) and single crystals x-ray diffraction. Three classes of complexes were obtained. Two of them are formed by complexes with mixed ligands, one at [VO(L)(OR) ] form, with R = methyl , ethyl , n- propyl and L = hydrazone , and the other one with the [VO(L)(mal)] empirical form, with L = hydrazone and mal = pyrone maltol. Another class consists of binuclear oxovanadium complexes obtained at [(VOL)2(μ-O)] form, with L = hydrazone and the vanadium centers connected by a μ-oxo bridge. The structures obtained for the mixed complexes with the alkoxides and dimers have quadratic distorted pyramidal geometry, while the mixed maltol complexes have distorted octahedral geometry.
In vitro assays against T. cruzi strains showed interesting results (SI equal to or greater than 10) to continue the exploration of the types of complexes formed and new biological tests must be conducted to verify the mechanism of action and in vivo activity of these compounds, in order to obtain a new vanadium-based antichagasic drug in the future.
 
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Publishing Date
2014-12-01
 
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