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Title: Potential of lichen secondary metabolites against Plasmodium liver stage parasites with FAS-II as the potential target
Authors: Lauinger, Ina L
Vivas, Livia
Perozzo, Remo
Stairiker, Christopher
Tarun, Alice
Zloh, Mire
Zhang, Xujie
Xu, Hua
Tonge, Peter J
Franzblau, Scott G
Pham, Duc Hung
Esguerra, Camila V
Crawford, Alexander D
Maes, Louis
Tasdemir, Deniz # ×
Issue Date: 28-Jun-2013
Publisher: American Society of Pharmacognosy
Series Title: Journal of Natural Products vol:76 issue:6 pages:1064-70
Article number: 10.1021/np400083k
Abstract: Chemicals targeting the liver stage (LS) of the malaria parasite are useful for causal prophylaxis of malaria. In this study, four lichen metabolites, evernic acid (1), vulpic acid (2), psoromic acid (3), and (+)-usnic acid (4), were evaluated against LS parasites of Plasmodium berghei. Inhibition of P. falciparum blood stage (BS) parasites was also assessed to determine stage specificity. Compound 4 displayed the highest LS activity and stage specificity (LS IC50 value 2.3 μM, BS IC50 value 47.3 μM). The compounds 1-3 inhibited one or more enzymes (PfFabI, PfFabG, and PfFabZ) from the plasmodial fatty acid biosynthesis (FAS-II) pathway, a potential drug target for LS activity. To determine species specificity and to clarify the mechanism of reported antibacterial effects, 1-4 were also evaluated against FabI homologues and whole cells of various pathogens (S. aureus, E. coli, M. tuberculosis). Molecular modeling studies suggest that lichen acids act indirectly via binding to allosteric sites on the protein surface of the FAS-II enzymes. Potential toxicity of compounds was assessed in human hepatocyte and cancer cells (in vitro) as well as in a zebrafish model (in vivo). This study indicates the therapeutic and prophylactic potential of lichen metabolites as antibacterial and antiplasmodial agents.
URI: 
ISSN: 0163-3864
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Biodiscovery (+)
× corresponding author
# (joint) last author

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