Spirocyclic Chromanes Exhibit Antiplasmodial Activities And Inhibit All Intraerythrocytic Life Cycle Stages
Keywords
Antimalarials; Antiplasmodials; Natural-product-like compounds; Novel mechanism of action; Spirocyclic chromane
Abstract
We screened a collection of synthetic compounds consisting of natural-product-like substructural motifs to identify a spirocyclic chromane as a novel antiplasmodial pharmacophore using an unbiased cell-based assay. The most active spirocyclic compound UCF 201 exhibits a 50% effective concentration (EC50) of 350 nM against the chloroquine-resistant Dd2 strain and a selectivity over 50 using human liver HepG2 cells. Our analyses of physicochemical properties of UCF 201 showed that it is in compliance with Lipinski's parameters and has an acceptable physicochemical profile. We have performed a limited structure-activity-relationship study with commercially available chromanes preserving the spirocyclic motif. Our evaluation of stage specificities of UCF 201 indicated that the compound is early-acting in blocking parasite development at ring, trophozoite and schizont stages of development as well as merozoite invasion. SPC is an attractive lead candidate scaffold because of its ability to act on all stages of parasite's aexual life cycle unlike current antimalarials.
Publication Date
4-1-2016
Publication Title
International Journal for Parasitology: Drugs and Drug Resistance
Volume
6
Issue
1
Number of Pages
85-92
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1016/j.ijpddr.2016.02.004
Copyright Status
Unknown
Socpus ID
84959234138 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/84959234138
STARS Citation
Roberts, Bracken F.; Iyamu, Iredia D.; Lee, Sukjun; Lee, Eunyoung; and Ayong, Lawrence, "Spirocyclic Chromanes Exhibit Antiplasmodial Activities And Inhibit All Intraerythrocytic Life Cycle Stages" (2016). Scopus Export 2015-2019. 3652.
https://stars.library.ucf.edu/scopus2015/3652