Title
Potential of Lichen secondary metabolites against plasmodium liver stage parasites with FAS-II as the potential target Potential of Lichen secondary metabolites against plasmodium liver stage parasites with FAS-II as the potential target
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Columbus, Ohio ,
Subject
Biology
Pharmacology. Therapy
Source (journal)
Journal of natural products. - Columbus, Ohio, 1979, currens
Volume/pages
76(2013) :6 , p. 1064-1070
ISSN
0163-3864
ISI
000321320600011
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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 mu M, BS IC50 value 47.3 mu M). The compounds 1 - 3 inhibited one Or more enzymes (Pf FabI, 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.,
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