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Scientific article
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Inhibition of Plasmodium falciparum Hsp90 Contributes to the Antimalarial Activities of Aminoalcohol-carbazoles

Published inJournal of medicinal chemistry, vol. 59, no. 13, p. 6344-6352
Publication date2016
Abstract

Malaria caused by the protozoan parasite Plasmodium falciparum (Pf) remains a major public health problem throughout the developing world. One molecular target that should receive more attention is the molecular chaperone Hsp90. It is essential and highly conserved in all eukaryotes, including in protozoan parasites. We have identified an aminoalcohol carbazole (N-CBZ) as a PfHsp90-selective inhibitor by virtually docking a large set of antimalarial compounds, previously found in a phenotypic screen, into a PfHsp90-specific pocket. By correlating the ability of 30 additional N-CBZ derivatives to bind directly to PfHsp90 with their Pf-inhibitory activity, we found that these types of compounds are more likely to inhibit Pf growth if they bind PfHsp90. For plausible targets such as PfHsp90, our workflow may help identifying the molecular target for compounds found by screening large chemical libraries for a desired biological effect and, conversely, ensuring biological effectiveness for compounds affecting a particular target.

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Citation (ISO format)
WANG, Tai, MÄSER, Pascal, PICARD, Didier. Inhibition of <i>Plasmodium falciparum</i> Hsp90 Contributes to the Antimalarial Activities of Aminoalcohol-carbazoles. In: Journal of medicinal chemistry, 2016, vol. 59, n° 13, p. 6344–6352. doi: 10.1021/acs.jmedchem.6b00591
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ISSN of the journal0022-2623
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