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Antimicrob Agents Chemother. 2015 Mar;59(3):1427-34. doi: 10.1128/AAC.04704-14. Epub 2014 Dec 15.

Small-molecule xenomycins inhibit all stages of the Plasmodium life cycle.

Author information

1
New York University School of Medicine, Department of Microbiology, Division of Parasitology, New York, New York, USA.
2
Roswell Park Cancer Institute, Department of Cell Stress Biology, Buffalo, New York, USA.
3
Incuron LLC, Buffalo, New York, USA.
4
New York University School of Medicine, Department of Microbiology, Division of Parasitology, New York, New York, USA ana.rodriguez@nyumc.org.

Abstract

Widespread resistance to most antimalaria drugs in use has prompted the search for novel candidate compounds with activity against Plasmodium asexual blood stages to be developed for treatment. In addition, the current malaria eradication programs require the development of drugs that are effective against all stages of the parasite life cycle. We have analyzed the antimalarial properties of xenomycins, a novel subclass of small molecule compounds initially isolated for anticancer activity and similarity to quinacrine in biological effects on mammalian cells. In vitro studies show potent activity of Xenomycins against Plasmodium falciparum. Oral administration of xenomycins in mouse models result in effective clearance of liver and blood asexual and sexual stages, as well as effective inhibition of transmission to mosquitoes. These characteristics position xenomycins as antimalarial candidates with potential activity in prevention, treatment and elimination of this disease.

PMID:
25512429
PMCID:
PMC4325811
DOI:
10.1128/AAC.04704-14
[Indexed for MEDLINE]
Free PMC Article

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