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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
Author(s) -
Sannella Anna Rosa,
Casini Angela,
Gabbiani Chiara,
Messori Luigi,
Bilia Anna Rita,
Vincieri Francesco Franco,
Majori Giancarlo,
Severini Carlo
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.02.028
Subject(s) - auranofin , plasmodium falciparum , thioredoxin reductase , pharmacology , oxidative stress , chemistry , in vitro , drug , antimalarial agent , toxicity , biochemistry , thioredoxin , medicine , malaria , immunology , rheumatoid arthritis , organic chemistry
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.