4 research outputs found
Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity
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 evidence of proteotoxic stress, violacein did not inhibit global protein synthesis via UPR activation - a process that is highly dependent on chaperones, in agreement with the notion of a violacein-induced proteostasis collapse. Our data highlight the importance of a functioning chaperone-proteasome system for parasite development and differentiation. Thus, a violacein-like small molecule might provide a good scaffold for development of a novel probe for examining the molecular chaperone network and/or antiplasmodial drug design.publishersversionpublishe
Phenolic and furanic compounds of Portuguese chestnut and French, American and Portuguese oak wood chips
Botanical species used on aging process must
be wisely and judiciously chosen, and for this selection, a
basic knowledge of the chemical composition of woods is
warranted. Aiming to contribute to extend the knowledge
of the chemical composition of several wood species useful
for enological purposes, we have focused our studies on
Portuguese chestnut and French, American and Portuguese
oak chips. The profile of low molecular weight phenolic
composition of these chips was achieved, using an optimized
extraction method based on pressurized liquid
extraction, followed by the quantification of phenolic acids,
phenolic aldehydes and furanic derivatives by high-performance
liquid chromatography (HPLC-DAD). The
identification of those compounds was also confirmed by
LC-DAD/ESI-MS. This study allowed the determination of
the low molecular phenolic composition of Portuguese
chestnut and French, American and Portuguese oak wood.
According to our results, the influence of the botanical
species seems to be more relevant than the geographic
origin of the wood species