Journal article
Histone deacetylase inhibitor AR-42 and achiral analogues kill malaria parasites in vitro and in mice
MJ Chua, J Tng, E Hesping, GM Fisher, CD Goodman, T Skinner-Adams, D Do, AJ Lucke, RC Reid, DP Fairlie, KT Andrews
International Journal for Parasitology Drugs and Drug Resistance | ELSEVIER SCI LTD | Published : 2021
Abstract
Malaria is caused by infection with Plasmodium parasites and results in significant health and economic impacts. Malaria eradication is hampered by parasite resistance to current drugs and the lack of a widely effective vaccine. Compounds that target epigenetic regulatory proteins, such as histone deacetylases (HDACs), may lead to new therapeutic agents with a different mechanism of action, thereby avoiding resistance mechanisms to current antimalarial drugs. The anticancer HDAC inhibitor AR-42, as its racemate (rac-AR-42), and 36 analogues were investigated for in vitro activity against P. falciparum. Rac-AR-42 and selected compounds were assessed for cytotoxicity against human cells, histo..
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Awarded by Griffith University
Funding Acknowledgements
This research was supported by the National Health and Medical Research Council of Australia (NHMRC Development Grant 1093378 to KTA and DPF; Senior Principal Research Fellowship 1117017 to DPF) . JT, AJL, DD, RCR and DPF thank the Australian Research Council Centre of Excellence for Advanced Molecular Imaging (grants CE140100011, DP180103244) for NMR, fluorescence and cell imaging support. MJC and EH thank Griffith University for providing academic scholarships (GUIPRS and GUPRS) .