Chemometric modeling, docking and in silico design of triazolopyrimidine-based dihydroorotate dehydrogenase inhibitors as antimalarials.

In the present work, QSAR and molecular docking studies have been performed on triazolopyrimidine-based dihydroorotate dehydrogenase (DHODH) inhibitors as antimalarial agents. The QSAR studies have been carried out using classical QSAR (physicochemical) approach using linear free energy related (LFER) model and molecular shape analysis using shape, spatial, electronic, thermodynamic and structural descriptors. Docking studies suggest that the 2-methyltriazolopyrimidine ring interacts with some polar and some nonpolar amino acids whereas the substituted phenyl ring binds with a hydrophobic pocket of the enzyme formed by some nonpolar amino acid residues. According to QSAR and molecular docking studies, we have designed some new compounds which showed good in silico predicted activity as per the developed QSAR models. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.