Artigo de Periódico
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
Autor
Silva, Thais Horta Álvares da
Oliveira, Marcelo Tavares de
Santos, Hélio Ferreira dos
Oliveira, Alaíde Braga de
Almeida, Wagner Batista de
Institución
Resumen
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. -