Planta Med 2013; 79 - PL14
DOI: 10.1055/s-0033-1348655

Discovering Novel Parasiticides Active Against Brugia pahangi from Filamentous Fungi

CJ Pearce 1, JN Clark 2, L Veasey 1, M Tillotson 1, B Darveaux 1, M Lawrence 1, NH Oberlies 3
  • 1Mycosynthetix, Inc., Hillsborough, NC 27275, USA
  • 2JNC Consulting, Pittsboro, NC 27312, USA
  • 3Department of Chemistry and Biochemistry, UNC Greensboro, NC 27412, USA

Mycosynthetix owns one of the largest libraries (55,000 strains) of filamentous fungi in the world. These organisms were isolated from substrates sourced from a wide variety of ecosystems and include many strains from tropical rain forests where there is a high degree of biodiversity. Our primary purpose is to exploit the medicinal and pharmaceutical potential of this large library. We have established validated whole organism assays to determine activity of fungal products against Haemonchus contortus, Cooperia onchophora, Stronglyoides stercoralis, Brugia pahangi (Bp) and Dirofilaria immitis microfilaria (Mf), L3 and L4 stages and Aedes aegypti larvae. There is little crossover of activity between the endo- and ectoparasites. Several compounds not only had high potency against BpMf but also caused high mortality within 24 hours. A small library of carefully selected purified fungal metabolites was tested in the BpMf assay at 50 ppm: a number of compounds were fully active at 3 – 6µM with the more potent showing nanomolar activity. One compound has shown potent activity against Bp L3 and L4 and DiL3, and several others are being tested. Results from several mammalian cell lines coupled with associated anti-parasitic data have identified compounds with high potency and a promising in vitro therapeutic index.