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The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.


ABSTRACT: The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca(2+), and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei.

SUBMITTER: Carvalho L 

PROVIDER: S-EPMC4576119 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.

Carvalho Luis L   Martínez-García Marta M   Pérez-Victoria Ignacio I   Manzano José Ignacio JI   Yardley Vanessa V   Gamarro Francisco F   Pérez-Victoria José M JM  

Antimicrobial agents and chemotherapy 20150720 10


The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submi  ...[more]

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