Portela César, Afonso Carlos M M, Pinto Madalena M M, Ramos Maria João
Centro de Estudos de Química Orgânica, Fitoquímica e Farmacologia da Universidade do Porto--Faculdade de Farmácia, Rua Aníbal Cunha, 164, 4050-047 Porto, Portugal.
J Comput Aided Mol Des. 2003 Sep;17(9):583-95. doi: 10.1023/b:jcam.0000005754.24588.a0.
One of the most important pharmacological mechanisms of antimalarial action is the inhibition of the aggregation of hematin into hemozoin. We present a group of new potential antimalarial molecules for which we have performed a DFT study of their stereoelectronic properties. Additionally, the same calculations were carried out for the two putative drug receptors involved in the referred activity, i.e., hematin mu-oxo dimer and hemozoin. A complementarity between the structural and electronic profiles of the planned molecules and the receptors can be observed. A docking study of the new compounds in relation to the two putative receptors is also presented, providing a correlation with the defined electrostatic complementarity.
