Química Nova (Mar 2005)

Estudo de modelagem molecular de complexos ferriprotoporfirina-IX e quinolinocarbinolaminas antimaláricas: proposta de um farmacóforo Molecular modeling study of complexes between ferriprotoporphyrin IX and antimalarial 4-quinolinecarbinolamines: a proposal of pharmacophore

  • Thais Horta Álvares da Silva,
  • Marcelo Tavares de Oliveira,
  • Hélio Ferreira dos Santos,
  • Alaíde Braga de Oliveira,
  • Wagner Batista De Almeida

DOI
https://doi.org/10.1590/S0100-40422005000200015
Journal volume & issue
Vol. 28, no. 2
pp. 244 – 249

Abstract

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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.

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