SAR and pharmacophore models for the rhodanine inhibitors of Plasmodium falciparum enoyl-acyl carrier protein reductase

IUBMB Life
Gyanendra KumarAvadhesha Surolia

Abstract

Significance of type II fatty acid synthase pathway in the life cycle of malarial parasite has long been established. Enoyl acyl carrier protein (ACP) reductase of Plasmodium falciparum (PfENR) is the rate determining enzyme of its elongation module. Hence, PfENR has been a target for the development of antimalarials as well as vaccines. Towards this endeavour, we had recently identified rhodanine class of compounds as inhibitors of PfENR. Here, we report a number of new inhibitors belonging to this class. These inhibitors have been divided into two broad subclasses: rhodanine-furans and rhodanine-phenyls. The inhibitory activity of all compounds was determined against purified PfENR. IC(50) of these compounds were found to be in nanomolar to low-micromolar range. The structure-activity relationship of both the classes has been explored in detail for the first time. Separate 3D pharmacophore models for this enzyme have been generated for both rhodanine furans and phenyls. The pharmacophore model for rhodanine furan has a Hydrogen bond donor, two Hydrogen bond acceptors, two metal ligators, three hydrophobic, and two aromatic ring features, whereas the pharmacophore model for the phenyl subclass has two hydrogen bond donors, two...Continue Reading

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Citations

Apr 11, 2012·Chemical Biology & Drug Design·Tabish Qidwai, Feroz Khan
Apr 7, 2015·Molecular and Biochemical Parasitology·Melanie J ShearsGeoffrey I McFadden
Nov 6, 2018·Frontiers in Cellular and Infection Microbiology·Cristian Rocha-RoaNéstor Cardona
Jul 1, 2020·International Journal of Molecular Sciences·Adriana R SilvaCassiano F Gonçalves-de-Albuquerque
May 15, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sahil KumarRajesh K Singh
Feb 9, 2021·Journal of Biomolecular Structure & Dynamics·David Bacelar Costa JúniorFranco Henrique Andrade Leite

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