Trypanosoma brucei, the causal agent for Human African Trypanosomiasis (HAT) also known as sleeping sickness, depends on ergosterol for growth. Here, we describe the effects of 26-fluorolanosterol (26FL), a mechanism-based inhibitor of T. brucei sterol C24-methyltransferase (24-SMT). 24-SMT is essential for sterol methylation and function of ergosterol in T. brucei, but is absent from the human host providing an opportunity for selective inhibition. 26FL showed potent inhibition of ergosterol biosynthesis and growth of procyclic and bloodstream forms of T. brucei while having no effect on cholesterol biosynthesis or growth of human epithelial kidney cells. These results demonstrate that inhibition of ergosterol biosynthesis by a 26-fluorinated Δ24-sterol is a promising strategy for developing a new treatment for trypanosomiasis.
|Publication status||Published - 2016|
|Event||American Chemical Society 72nd Southwest Regional Meeting: Innovations in Energy and Medicine - Galveston, United States|
Duration: 10 Nov 2016 → 13 Nov 2016
|Conference||American Chemical Society 72nd Southwest Regional Meeting|
|Period||10/11/16 → 13/11/16|