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New uses for old drugs. Auranofin, a clinically established antiarthritic metallodrug, exhibits potent antimalarial effects in vitro: mechanistic and pharmacological implications

Sannella, Anna Rosa, Casini, Angela, Gabbiani, Chiara, Messori, Luigi, Bilia, Anna Rita, Vincieri, Francesco Franco, Majori, Giancarlo and Severini, Carlo 2008. New uses for old drugs. Auranofin, a clinically established antiarthritic metallodrug, exhibits potent antimalarial effects in vitro: mechanistic and pharmacological implications. FEBS Letters 582 (6) , pp. 844-847. 10.1016/j.febslet.2008.02.028

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Abstract

The clinically established gold-based antiarthritic drug auranofin (AF) manifests a pronounced reactivity toward thiol and selenol groups of proteins. In particular, AF behaves as a potent inhibitor of mammalian thioredoxin reductases causing severe intracellular oxidative stress. Given the high sensitivity of Plasmodium falciparum to oxidative stress, we thought that auranofin might act as an effective antimalarial agent. Thus, we report here new experimental results showing that auranofin and a few related gold complexes strongly inhibit P. falciparum growth in vitro. The observed antiplasmodial effects probably arise from direct inhibition of P. falciparum thioredoxin reductase. The above findings and the safe toxicity profile of auranofin warrant rapid evaluation of AF for malaria treatment in animal models.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Elsevier
Date of Acceptance: 14 February 2008
Last Modified: 04 Jun 2017 08:30
URI: http://orca.cf.ac.uk/id/eprint/79365

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