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Master's Dissertation
DOI
10.11606/D.46.2014.tde-21012015-085103
Document
Author
Full name
Gustavo Levendoski Sabino
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Ferreira, Ana Maria da Costa (President)
Alves, Maria Julia Manso
Batista, Alzir Azevedo
Title in Portuguese
Investigação da reatividade de complexos metálicos com ligantes bases de Schiff frente a infecções parasitárias
Keywords in Portuguese
Atividade antiparasitária
Cobre
Doença de Chagas
Trypanosoma cruzi
Zinco
Abstract in Portuguese
Ligantes oxindolimínicos foram sintetizados através de procedimentos já desenvolvidos em nosso laboratório, a partir do 2,3-dioxindol (isatina) e aminas ou diaminas selecionadas, e em seguida metalados. Foram investigados dois complexos de cobre(II) com os ligantes isaepy, preparado a partir de 2-(2-aminoetilpiridina) e isapn, a partir de 1,2-diaminoetano, e os correspondentes complexos de zinco(II). Após caracterização por diversas técnicas, sua reatividade com relação a biomoléculas (HSA e DNA) foi verificada, através de medidas de fluorescência e dicroísmo circular. Posteriormente, sua reatividade antiparasitária frente a T. cruzi foi testada. Todos eles apresentaram atividade tóxica frente às formas tripomastigota e amastigota do parasita, com índices de seletividade bastante promissores, quando comparados à droga atualmente em uso (benzonidazol) e outras alternativas descritas na literatura. Anteriormente estes complexos já haviam demonstrado atividade pró-apoptótica frente a diversas células tumorais, baseado em sua capacidade de gerar espécies reativas (EROs) e de inibir proteínas específicas, como a topoisomerase humana IB. Os resultados aqui obtidos deram origem a um pedido de patente (BR10 2013 026558-6, depositado junto ao INPI em 15/outubro/2013) visando o possível desenvolvimento de novos fármacos para a doença de Chagas.
Title in English
Investigations on the reactivity of metal complexes with Schiff-base ligands towards parasite infections
Keywords in English
Chagas disease
Copper
Trypanocidal activity
Trypanosoma cruzi
Zinc
Abstract in English
Oxindolimine ligands were synthesized by procedures previously developed in our laboratory, from 2,3-dioxoindole(isatin) and amines or selected diamines, by condensation reactions, followed by metallation. Two copper(II) complexes with isaepy and isapn ligands, prepared from 2-(2-aminoethylpiridine) and 1,2-diaminoethane respectively, and their corresponding complexes of zinc(II) were investigated. After characterization by various techniques, their reactivity with respect to biomolecules (HSA and DNA) was verified, through measurements of fluorescence and circular dichroism. Subsequently, their antiparasitary reactivity against T. cruzi was tested. All complexes tested presents toxic activity against trypomastigote and amastigote forms of the parasite, with promising selectivity index, compared to drugs currently in use (benznidazole) and other alternative compounds described in literature. Previously, these complexes had shown pro-apoptotic activity against several tumor cells, based on their ability to generate reactive species and inhibit specific proteins, such as topoisomerases. The results obtained here gave rise to a patent application (BR10 2013 026558-6, deposited on INPI in October 15th, 2013), looking for a possible development of new drugs for Chagas disease.
 
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Publishing Date
2015-03-23
 
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