Trojan horse inhibition of ergosterol biosynthesis and growth in Trypanosoma brucei by fluorinated sterols

David Leaver; Presheet Patkar; Ujjal Singha; Matthew Miller; Brad Haubrich; Minu Chaudhuri; W. David Nes

Trojan horse inhibition of ergosterol biosynthesis and growth in Trypanosoma brucei by fluorinated sterols

David Leaver (Presenter), Presheet Patkar, Ujjal Singha, Matthew Miller, Brad Haubrich, Minu Chaudhuri, W. David Nes

Research output: Other contribution to conference › Poster › peer-review

Abstract

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.

Original language	English
Publication status	Published - 2016
Externally published	Yes
Event	American Chemical Society 72nd Southwest Regional Meeting: Innovations in Energy and Medicine - Galveston, United States Duration: 10 Nov 2016 → 13 Nov 2016

Conference

Conference	American Chemical Society 72nd Southwest Regional Meeting
Country/Territory	United States
City	Galveston
Period	10/11/16 → 13/11/16

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

@conference{c7aa6a461b7c48f78919ba9cd66799c5,

title = "Trojan horse inhibition of ergosterol biosynthesis and growth in Trypanosoma brucei by fluorinated sterols",

abstract = "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.",

author = "David Leaver and Presheet Patkar and Ujjal Singha and Matthew Miller and Brad Haubrich and Minu Chaudhuri and Nes, {W. David}",

year = "2016",

language = "English",

note = "American Chemical Society 72nd Southwest Regional Meeting : Innovations in Energy and Medicine ; Conference date: 10-11-2016 Through 13-11-2016",

}

Trojan horse inhibition of ergosterol biosynthesis and growth in Trypanosoma brucei by fluorinated sterols. / Leaver, David (Presenter); Patkar, Presheet; Singha, Ujjal et al.
2016. Poster session presented at American Chemical Society 72nd Southwest Regional Meeting, Galveston, Texas, United States.

Research output: Other contribution to conference › Poster › peer-review

TY - CONF

T1 - Trojan horse inhibition of ergosterol biosynthesis and growth in Trypanosoma brucei by fluorinated sterols

AU - Patkar, Presheet

AU - Singha, Ujjal

AU - Miller, Matthew

AU - Haubrich, Brad

AU - Chaudhuri, Minu

AU - Nes, W. David

A2 - Leaver, David

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

M3 - Poster

T2 - American Chemical Society 72nd Southwest Regional Meeting

Y2 - 10 November 2016 through 13 November 2016

ER -

Trojan horse inhibition of ergosterol biosynthesis and growth in Trypanosoma brucei by fluorinated sterols

Abstract

Conference

UN SDGs

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