Potential of Lichen Secondary Metabolites against Plasmodium Liver Stage Parasites with FAS-II as the Potential Target

Lauinger, IL; Vivas, L; Perozzo, R; Stairiker, C; Tarun, A; Zloh, M; Zhang, XJ; Xu, H; Tonge, PJ; Franzblau, SG; Pham, DH; Esguerra, CV; Crawford, AD; Maes, L; Tasdemir, D; (2013) Potential of Lichen Secondary Metabolites against Plasmodium Liver Stage Parasites with FAS-II as the Potential Target. Journal of natural products, 76 (6). pp. 1064-1070. ISSN 0163-3864 DOI: https://doi.org/10.1021/np400083k

Full text not available from this repository.


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.

Item Type: Article
Keywords: fatty-acid biosynthesis, carrier protein reductase, enoyl-acp reductase, usnic acid, in-vitro, antimycobacterial activity, staphylococcus-aureus, antimalarial activity, drug discovery, falciparum
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
PubMed ID: 23806111
Web of Science ID: 321320600011
URI: http://researchonline.lshtm.ac.uk/id/eprint/1229441


Download activity - last 12 months
Downloads since deposit
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item