edoc

Inhibition of Plasmodium falciparum Hsp90 contributes to the antimalarial activities of aminoalcohol-carbazoles

Wang, Tai and Mäser, Pascal and Picard, Didier. (2016) Inhibition of Plasmodium falciparum Hsp90 contributes to the antimalarial activities of aminoalcohol-carbazoles. Journal of Medicinal Chemistry, 59 (13). pp. 6344-6352.

[img]
Preview
PDF - Published Version
3846Kb

Official URL: http://edoc.unibas.ch/44577/

Downloads: Statistics Overview

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 amino-alcohol 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Mäser, Pascal
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
ISSN:0022-2623
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:18 Oct 2017 08:21
Deposited On:17 Nov 2016 10:41

Repository Staff Only: item control page