In:
Molecular Informatics, Wiley, Vol. 32, No. 7 ( 2013-07), p. 659-670
Abstract:
Cytochrome bc 1 complex is a crucial element in the mitochondrial respiratory chain, being indispensable for the survival of several species of Plasmodia that cause malaria and, therefore, it is a promising target for antimalarial drug development. We report a molecular docking study building on the most recently obtained X‐ray structure of the Saccharomyces cerevisiae bc 1 complex (PDB code: 3CX5) using several reported inhibitors with experimentally determined IC 50 values against the Plasmodium falciparum bc 1 complex. We produced a molecular docking model that correlated the calculated binding free energy with the experimental inhibitory activity of each compound. This Q o model was used to search the drug‐like database included in the MOE package for novel potential bc 1 complex inhibitors. Twenty three compounds were chosen to be tested for their antimalarial activity and four of these compounds demonstrated activity against the chloroquine‐resistant W2 strain of P. falciparum . The most active compounds were also active against the atovaquone‐resistant P. falciparum FCR3 strain and S. cerevisiae . Our study suggests the validity of the yeast bc 1 complex structure as a model for the discovery of new antimalarial hits.
Type of Medium:
Online Resource
ISSN:
1868-1743
,
1868-1751
DOI:
10.1002/minf.201300024
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2537668-8
SSG:
15,3
