Novel Endoperoxide Antimalarials: Synthesis, Heme Binding, and Antimalarial Activity

Title
Novel Endoperoxide Antimalarials: Synthesis, Heme Binding, and Antimalarial Activity
Publication Date
2004
Author(s)
Taylor, Dennis K
Avery, Thomas D
Tilley, Leann
Greatrex, Ben
( author )
OrcID: https://orcid.org/0000-0002-0356-4966
Email: bgreatre@une.edu.au
UNE Id une-id:bgreatre
Tiekink, Edward R T
Macreadie, Ian G
Macreadie, Peter I
Humphries, Adam D
Kalkanidis, Martha
Fox, Emma N
Klonis, Nectarios
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
American Chemical Society
Place of publication
United States of America
DOI
10.1021/jm0305319
UNE publication id
une:15729
Abstract
We report the synthesis of a series of novel epoxy endoperoxide compounds that can be prepared in high yields in one to three steps from simple starting materials. Some of these compounds inhibit the growth of 'Plasmodium falciparum' in vitro. Structure-activity studies indicate that an endoperoxide ring bisubstituted with saturated cyclic moieties is the pharmacophore. To study the molecular basis of the action of these novel antimalarial compounds, we examined their ability to interact with oxidized and reduced forms of heme. Some of the compounds interact with oxidized heme in a fashion similar to chloroquine and other 4-aminoquinolines, while some of the compounds interact with reduced heme. However, the level of antimalarial potency is not well correlated with these activities, suggesting that some of the endoperoxides may exert their antimalarial activities by a novel mechanism of action.
Link
Citation
Journal of Medicinal Chemistry, 47(7), p. 1833-1839
ISSN
1520-4804
0022-2623
Start page
1833
End page
1839

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