Title :

Effect of clinically approved HDAC inhibitors on Plasmodium, Leishmania and Schistosoma parasite growth.

Author(s) :

Chua, Ming Jang [Auteur]
Griffith University [Brisbane]
Arnold, Megan S J [Auteur]
Griffith University [Brisbane]
Xu, Weijun [Auteur]
Institute for Molecular Bioscience
Lancelot, Julien [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Lamotte, Suzanne [Auteur]
Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling
Späth, Gerald F [Auteur]
Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling
Prina, Eric [Auteur]
Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling
Pierce, Raymond J [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Fairlie, David P [Auteur]
Institute for Molecular Bioscience
Skinner-Adams, Tina S [Auteur]
Griffith University [Brisbane]
Andrews, Katherine T [Auteur correspondant]
Griffith University [Brisbane]

Journal title :

International journal for parasitology. Drugs and drug resistance

Pages :

42-50

Publisher :

Elsevier

Publication date :

2017-04

ISSN :

2211-3207

English keyword(s) :

Histone deacetylase
Leishmania
Panobinostat
Plasmodium
Schistosoma

HAL domain(s) :

Sciences du Vivant [q-bio]/Microbiologie et Parasitologie

English abstract : [en]

Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene ...
Show more >Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model. All four compounds were potent inhibitors of P. knowlesi malaria parasites (IC50 9-370 nM), with belinostat, panobinostat and vorinostat having 8-45 fold selectivity for the parasite over human neonatal foreskin fibroblast (NFF) or human embryonic kidney (HEK 293) cells, while romidepsin was not selective. Each of the HDAC inhibitor drugs caused hyperacetylation of P. knowlesi histone H4. None of the drugs was active against Leishmania amastigote or promastigote parasites (IC50 > 20 μM) or S. mansoni schistosomula (IC50 > 10 μM), however romidepsin inhibited S. mansoni adult worm parings and egg production (IC50 ∼10 μM). Modest in vivo activity was observed in P. berghei infected mice dosed orally with vorinostat or panobinostat (25 mg/kg twice daily for four days), with a significant reduction in parasitemia observed on days 4-7 and 4-10 after infection (P < 0.05), respectively.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

European Project :

Anti-Parasitic Drug Discovery in Epigenetics

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL