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Estudo de modelagem molecular de complexos ferriprotoporfirina-IX e quinolinocarbinolaminas antimaláricas: proposta de um farmacóforo

2005; Brazilian Chemical Society; Volume: 28; Issue: 2 Linguagem: Inglês

10.1590/s0100-40422005000200015

ISSN

1678-7064

Autores

Thais Horta Álvares da Silva, Marcelo Tavares de Oliveira, Hélio Ferreira Dos Santos, Alaı́de Braga de Oliveira, Wagner Batista De Almeida,

Tópico(s)

Multicomponent Synthesis of Heterocycles

Resumo

A PROPOSAL OF PHARMACOPHORE.Quinine and quinidine are well-known 4quinolinecarbinolamines that exhibit antimalarial activity, but, in contrast, their epimers 9-epiquinine and 9-epiquinidine are almost inactive.Literature data are conflicting in describing the 4-quinolinecarbinolamine interaction mode with the molecular target, the ferriprotoporphyrin IX [Fe(III)PPIX].In the present paper, a pharmacophore is proposed based on the binding of the nonaromatic nitrogen to the iron atom.The 4-quinolinecarbinolamine antimalarials were superimposed on the pharmacophore under consideration and complexes with Fe(III)PPIX were constructed.Conformational analyses of the complexes were performed applying the MM+ molecular mechanics method.The analysis of the complexes showed that the proposed ligand mode is possible although it does not explain the activity differences between epimers.A discussion of the structural aspects is also provided.

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