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© Jean-Claude Antoine
Leishmania mexicana amazonensis
Publication : International journal for parasitology. Drugs and drug resistance

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in International journal for parasitology. Drugs and drug resistance - 23 Dec 2016

Chua MJ, Arnold MS, Xu W, Lancelot J, Lamotte S, Späth GF, Prina E, Pierce RJ, Fairlie DP, Skinner-Adams TS, Andrews KT

Link to Pubmed [PMID] – 28107750

Int J Parasitol Drugs Drug Resist 2017 04;7(1):42-50

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 (IC 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 (IC > 20 μM) or S. mansoni schistosomula (IC > 10 μM), however romidepsin inhibited S. mansoni adult worm parings and egg production (IC ∼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.

https://www.ncbi.nlm.nih.gov/pubmed/28107750