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

• Autor(a) principal: Silva,Thais Horta Álvares da
• Data de Publicação: 2005
• Outros Autores: Oliveira,Marcelo Tavares de, Santos,Hélio Ferreira dos, Oliveira,Alaíde Braga de, De Almeida,Wagner Batista
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Química Nova (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-40422005000200015
• topic: antimalarial; quinine; pharmacophore

Quinine and quinidine are well-known 4-quinolinecarbinolamines 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 non-aromatic 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.