Discovery of new potential hits of Plasmodium falciparum enoyl-ACP reductase through ligand- and structure-based drug design approaches

被引：21

作者：

Neves, Bruno J. ^{[1
]}

Bueno, Renata V. ^{[1
]}

Braga, Rodolpho C. ^{[1
]}

Andrade, Carolina H. ^{[1
]}

机构：

[1] Univ Fed Goias, Fac Farm, Lab Planejamento Farmacos & Estudos Metab Modelag, BR-74605220 Goiania, Go, Brazil

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 08期

关键词：

Enoyl-ACP reductase; Plasmodium falciparum; Drug design; QSAR; New inhibitors; CARRIER PROTEIN REDUCTASE; DIFFERENT ALIGNMENT METHODS; MOLECULAR TARGETS; 3D QSAR; INHIBITORS; MALARIA; TRICLOSAN; VALIDATION; PROSPECTS; PROGRESS;

D O I：

10.1016/j.bmcl.2013.02.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：2436 / 2441

页数：6

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