Antimalarials from Plant Pathogenic Fungi

Malaria is a serious infectious disease. Drug resistance in parasites and insecticide resistance in mosquito vector limit control of malaria. Therefore, there is an urgent need to search for new drugs with new modes of action. Plant-like metabolic pathways found in the apicoplast of Plasmodium species have been identified as suitable targets in malaria drug discovery [1]. Certain herbicides and phytotoxins released by plant pathogenic fungi are known to inhibit metabolic pathways in the apicoplast [2]. Furthermore, metabolites from endophytes including plant pathogenic fungi may also target other metabolic pathways in malaria parasites. As part of our ongoing screening program for potential antimalarials, we have screened ethyl acetate extracts of the fermentation culture of plant pathogenic fungi obtained from American Type Culture Collection (ATCC) and from diseased leaves of the conifer, Torreya taxifolia Arnott. Some of the compounds isolated from these fungi showed potent antiplasmodial and phytotoxic activities with no cytotoxicity to mammalian cells. However, these compounds do not appear to target metabolic pathways of the apicoplast. Acknowledgements: This work was supported by the National Institutes of Health (R21 A1061431 – 01) and in part by the United States Department of Agriculture, ARS, Specific Cooperative Agreement No. 58 – 6408 – 02 – 1-612. The authors sincerely thank Dr. Bharathi Avula and Mr. F. T. Wiggers for recording the MS and ¹H NMR spectra (600 MHz), and Mr. John Trott for biological testing. References: [1] Lichtenthaler HK, (2000) Biochem Soc Trans, 28: 785 – 789 (2) Bajsa J, Singh K. et al. (2007) Bio Pharm Bull, 30: 1740 – 1744.