Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 23, Issue 8, Pages 2436-2441Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2013.02.006
Keywords
Enoyl-ACP reductase; Plasmodium falciparum; Drug design; QSAR; New inhibitors
Categories
Funding
- CNPq
- CAPES
- FAPEG
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We here report the discovery of novel Plasmodium falciparum enoyl-ACP reductase (PfENR) inhibitors as new antimalarial hits through ligand-and structure-based drug design approaches. We performed 2D and 3D QSAR studies on a set of rhodanine analogues using hologram QSAR (HQSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Statistical and satisfactory results were obtained for the best HQSAR (r(2) of 0.968 and q(LOO)(2) of 0.751), CoMFA (r(2) of 0.955 and q(LOO)(2) of 0.806) and CoMSIA (r(2) of 0.965 and q(LOO)(2) of 0.659) models. The information gathered from the QSAR models guided us to design new PfENR inhibitors. Three new hits were predicted with potency in the submicromolar range and presented drug-like properties. (C) 2013 Elsevier Ltd. All rights reserved.
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