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

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.

Bibliographic Details

Main Authors:	Silva,Thais Horta Álvares da, Oliveira,Marcelo Tavares de, Santos,Hélio Ferreira dos, Oliveira,Alaíde Braga de, De Almeida,Wagner Batista
Format:	Digital revista
Language:	Portuguese
Published:	Sociedade Brasileira de Química 2005
Online Access:	http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-40422005000200015
Tags:	Add Tag No Tags, Be the first to tag this record!