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1.
J Med Chem ; 55(9): 4231-43, 2012 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-22443115

RESUMO

The in vitro and in vivo anti- Trypanosoma cruzi activity of the pyrazole-containing macrobicyclic polyamine 1 and N-methyl- and N-benzyl-substituted monocyclic polyamines 2 and 3 was studied. Activity against both the acute and chronic phases of Chagas disease was considered. The compounds were more active against the parasite and less toxic against Vero cells than the reference drug benznidazole, but 1 and 2 were especially effective, where cryptand 1 was the most active, particularly in the chronic phase. The activity results found for these compounds were complemented and discussed by considering their inhibitory effect on the iron superoxide dismutase enzyme of the parasite, the nature of the metabolites excreted after treatment, and the ultrastructural alterations produced. A complementary histopathological analysis confirmed that the compounds tested were significantly less toxic to mammals than the reference drug and that 1 and 2 exhibited lower levels of damage than 3.


Assuntos
Doença de Chagas/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Poliaminas/farmacologia , Pirazóis/farmacologia , Tripanossomicidas/síntese química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Doença de Chagas/parasitologia , Chlorocebus aethiops , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Feminino , Humanos , Fígado/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Poliaminas/síntese química , Poliaminas/química , Pirazóis/síntese química , Pirazóis/química , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/metabolismo , Tripanossomicidas/química , Trypanosoma cruzi/enzimologia , Células Vero
2.
J Phys Chem B ; 113(43): 14465-72, 2009 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-19813710

RESUMO

The structural, tautomeric, hydrogen-bonding, stacking, and electronic properties of a seleno-derivative of thymine (T), denoted here as 4SeT and created by replacing O4 in T with Se, are investigated by means of ab initio computational techniques. The structural properties of T and 4SeT are very similar, and the geometrical differences are mainly limited to the adjacent environment of the C-Se bond. The canonical "keto" form is the most stable tautomer, in the gas phase and in aqueous solution, for both T and 4SeT. It is argued that the competition between two opposite trends, i.e., a decrease in the base-pairing ability and an increase of the stacking interaction upon incorporation of 4SeT into a duplex, likely explains the similar experimental melting points of a seleno-derivative duplex (Se-DNA) and its native counterpart. Interestingly, the underlying electronic structure shows that replacement of O4 with Se promotes a reduction in the HOMO-LUMO gap and an increase in interplane coupling, which suggests that Se-DNA could be potentially useful for nanodevice applications. This finding is further supported by the fact that transfer integrals between 4SeT...A stacked base pairs are larger than those determined for similarly stacked natural T...A pairs.


Assuntos
Selênio/química , Pareamento de Bases , Ligação de Hidrogênio , Conformação Molecular , Eletricidade Estática , Termodinâmica , Timina/química
3.
Trib. estomatol ; 1(4): 64-67, nov. 2003. ilus
Artigo em Espanhol | LIPECS | ID: biblio-1112275

RESUMO

La terapia bioprogresiva es una filosofía que acepta como misión el tratamiento de toda la cara y no solo el objetivo de los dientes y la oclusión. Aunque estos son de importancia critica para lograr el objetivo mas amplio de tratar y mejorar la cara, los tratamientos ortodóncicos deben ser diseñados para ser aplicados de manera adecuada a los tipos faciales, los patrones musculares y las necesidades funcionales específicas de los individuos.


Assuntos
Feminino , Criança , Humanos , Arco Dental , Terapia Biológica
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