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https://hdl.handle.net/1959.11/15500
Title: | Novel Endoperoxide Antimalarials: Synthesis, Heme Binding, and Antimalarial Activity | Contributor(s): | Taylor, Dennis K (author); Avery, Thomas D (author); Tilley, Leann (author); Greatrex, Ben (author) ; Tiekink, Edward R T (author); Macreadie, Ian G (author); Macreadie, Peter I (author); Humphries, Adam D (author); Kalkanidis, Martha (author); Fox, Emma N (author); Klonis, Nectarios (author) | Publication Date: | 2004 | DOI: | 10.1021/jm0305319 | Handle Link: | https://hdl.handle.net/1959.11/15500 | 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. | Publication Type: | Journal Article | Source of Publication: | Journal of Medicinal Chemistry, 47(7), p. 1833-1839 | Publisher: | American Chemical Society | Place of Publication: | United States of America | ISSN: | 1520-4804 0022-2623 |
Fields of Research (FoR) 2008: | 030401 Biologically Active Molecules 030503 Organic Chemical Synthesis |
Socio-Economic Objective (SEO) 2008: | 970103 Expanding Knowledge in the Chemical Sciences 929999 Health not elsewhere classified 970106 Expanding Knowledge in the Biological Sciences |
Peer Reviewed: | Yes | HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
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Appears in Collections: | Journal Article |
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