Discovery of small molecule inhibitors of Hsp90 chaperone.

Leishmaniasis is a neglected disease caused by the protozoa . Environmental differences found by the parasites in the vector and the host are translated into cellular stress, leading to the production of heat shock proteins (Hsp). These are molecular chaperones involved in the folding of nascent proteins as well as in the regulation of gene expression, signalling events and proteostasis. Since . use Hsp90 to trigger important transitions between their different stages of the life cycle, this protein family becomes a profitable target in anti-parasite drug discovery. In this work, we implemented a multidisciplinary strategy coupling molecular modelling with assays to identify small molecules able to inhibit Hsp90 from (LbHsp90). Overall, we identified some compounds able to kill the promastigote form of the , and to inhibit LbHsp90 ATPase activity.