Mechanism of antimalarial action of the synthetic trioxolane RBX11160 (OZ277)
Language: 
English
Abstract: 

RBX11160 (OZ277) is a fully synthetic peroxidic antimalarial in clinical development. To study the possible mechanisms of action of RBX11160, we have examined its ability to inhibit PfATP6, a sarcoplasmic reticulum calcium ATPase and proposed target for semisynthetic peroxidic artemisinin derivatives. RBX11160 inhibits PfATP6 (apparent half-maximal inhibitory constant=7,700 nM) less potently than artemisinin (79 nM). Inhibition of PfATP6 is abrogated by desferrioxamine, an iron-chelating agent. Consistent with this finding, the killing of Plasmodium falciparum organisms by RBX11160 in vitro is antagonized by desferrioxamine. Artesunate and RBX11160 also act antagonistically against P. falciparum in vitro. A fluorescent derivative of RBX11160 localizes to the parasite cytosol in some parasites and to the food vacuole in other parasites. These data demonstrate that there are both similarities and differences between the antimalarial properties of RBX11160 and those of semisynthetic antimalarials such as artesunate and artemisinin.

Author(s): 
Uhlemann, Anne-Catrin
Wittlin, Sergio
Matile, Hugues
Bustamante, Leyla Y.
Krishna, Sanjeev
Item Type: 
Journal Article
Publication Title: 
Antimicrobial Agents and Chemotherapy
Journal Abbreviation: 
Antimicrob. Agents Chemother.
Publication Date: 
2/7/2015
Publication Year: 
2007
Pages: 
667-672
Volume: 
51
Issue: 
2
ISSN: 
0066-4804
DOI: 
10.1128/AAC.01064-06
Library Catalog: 
PubMed
Extra: 
PMID: 17145800 PMCID: PMC1797759

Turabian/Chicago Citation

Anne-Catrin Uhlemann, Sergio Wittlin, Hugues Matile, Leyla Y. Bustamante and Sanjeev Krishna. 2/7/2015. "Mechanism of antimalarial action of the synthetic trioxolane RBX11160 (OZ277)." Antimicrobial Agents and Chemotherapy 51: 2: 667-672. 10.1128/AAC.01064-06.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1128/AAC.01064-06 | issn = 0066-4804 | volume = 51 | pages = 667-672 | last = Uhlemann | first = Anne-Catrin | coauthors = Wittlin, Sergio, Matile, Hugues, Bustamante, Leyla Y., Krishna, Sanjeev | title = Mechanism of antimalarial action of the synthetic trioxolane RBX11160 (OZ277) | journal = Antimicrobial Agents and Chemotherapy | date = 2/7/2015 | pmid = | pmc = }} </ref>