Potential of lichen secondary metabolites againstplasmodiumliver stage parasites with fas-ii as the potential target
Lauinger, Ina L.
Tonge, Peter J.
Franzblau, Scott G.
Esguerra, Camila V.
Crawford, Alexander D.
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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 (2013). Potential of lichen secondary metabolites againstplasmodiumliver stage parasites with fas-ii as the potential target. Journal of Natural Products 76 (6), 1064-1070
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.,