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Title
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Potential of Lichen secondary metabolites against plasmodium liver stage parasites with FAS-II as the potential target
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Author
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Abstract
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| 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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Language
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English
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Source (journal)
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Journal of natural products. - Columbus, Ohio, 1979, currens
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Publication
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Columbus, Ohio
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2013
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ISSN
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0163-3864
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DOI
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10.1021/NP400083K
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Volume/pages
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76
:6
(2013)
, p. 1064-1070
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ISI
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000321320600011
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Full text (Publisher's DOI)
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