Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity.

ABSTRACT: Antimalarial drugs with novel modes of action and wide therapeutic potential are needed to pave the way for malaria eradication. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, Plasmodium falciparum (Pf). Herein, using chemical genomic profiling (CGP), we found that violacein affects protein homeostasis. Mechanistically, violacein binds Pf chaperones, PfHsp90 and PfHsp70-1, compromising the latter's ATPase and chaperone activities. Additionally, violacein-treated parasites exhibited increased protein unfolding and proteasomal degradation. The uncoupling of the parasite stress response reflects the multistage growth inhibitory effect promoted by violacein. Despite eviden

SUBMITTER: Tavella TA 

PROVIDER: S-EPMC8042658 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature