Synthesis of fluorinated sterols and trojan horse inhibition of ergosterol biosynthesis in Trypanosoma brucei

David Leaver

Synthesis of fluorinated sterols and trojan horse inhibition of ergosterol biosynthesis in Trypanosoma brucei

Charles Sturt University

Research output: Other contribution to conference › Presentation only

Abstract

The causative agent for Human African Trypanosomiasis (HAT) is Trypanosoma brucei and it is noted that this protozoan parasite is dependent on ergosterol for growth. 26-Fluorolanosterol (26FL) and 26-fluorocholesta-5,7,24-trienol (26-FCT) were observed to be irreversible (mechanism-based) inhibitors of the T. brucei sterol C24-methyltransferase (24-SMT). 24-SMT is an essential enzyme for T. brucei, however, this enzyme is not found in the human host, which makes inhibiting 24-SMT with small molecules an attractive therapeutic strategy. The synthesis of 26FL and 26-FCT will be discussed in addition to their ability to poison ergosterol biosynthesis in T. brucei.

Original language	English
Publication status	Published - 2025
Event	The 16th International Meeting on Biosynthesis, Function and Synthetic Biology of Isoprenoids: TERPNET 2025 - Rydges South Bank Brisbane, Brisbane, Australia Duration: 04 Aug 2025 → 08 Aug 2025 https://web-eur.cvent.com/event/4b2cc1fa-86f3-4087-903f-f9a2fb2b2ef7/summary?rt=4sXcuNICaU2liaSNEcQuUQ

Conference

Conference	The 16th International Meeting on Biosynthesis, Function and Synthetic Biology of Isoprenoids
Country/Territory	Australia
City	Brisbane
Period	04/08/25 → 08/08/25
Other	TERPNET is an international confederation of researchers aligned for the advancement of all scientific pursuits related to terpenes, terpenoids and isoprenoids including Biosynthesis, Function, Biological activities, industrial applications and Synthetic Biology. The conference runs every two years and rotates between America, Europe, and Asia. For the first time this year the meeting will be held in Australia (Brisbane). The 16th edition of TERPNET is co-Chaired by Prof. Claudia Vickers and Dr Jordi Perez-Gil.
Internet address	https://web-eur.cvent.com/event/4b2cc1fa-86f3-4087-903f-f9a2fb2b2ef7/summary?rt=4sXcuNICaU2liaSNEcQuUQ

1 Article

Fluorinated Sterols Are Suicide Inhibitors of Ergosterol Biosynthesis and Growth in Trypanosoma brucei
Leaver, D. J., Patkar, P., Singha, U., Miller, M., Haubrich, B., Chaudhuri, M. & Nes, W. D., 2015, In: Chemistry and Biology. 22, 10, p. 1374-1383
Research output: Contribution to journal › Article › peer-review
16 Citations (Scopus)

Cite this

@conference{abc09e72abdb4a139878d4303669cdb8,

title = "Synthesis of fluorinated sterols and trojan horse inhibition of ergosterol biosynthesis in Trypanosoma brucei",

abstract = "The causative agent for Human African Trypanosomiasis (HAT) is Trypanosoma brucei and it is noted that this protozoan parasite is dependent on ergosterol for growth. 26-Fluorolanosterol (26FL) and 26-fluorocholesta-5,7,24-trienol (26-FCT) were observed to be irreversible (mechanism-based) inhibitors of the T. brucei sterol C24-methyltransferase (24-SMT). 24-SMT is an essential enzyme for T. brucei, however, this enzyme is not found in the human host, which makes inhibiting 24-SMT with small molecules an attractive therapeutic strategy. The synthesis of 26FL and 26-FCT will be discussed in addition to their ability to poison ergosterol biosynthesis in T. brucei.",

author = "David Leaver",

year = "2025",

language = "English",

note = "The 16th International Meeting on Biosynthesis, Function and Synthetic Biology of Isoprenoids : TERPNET 2025 ; Conference date: 04-08-2025 Through 08-08-2025",

url = "https://web-eur.cvent.com/event/4b2cc1fa-86f3-4087-903f-f9a2fb2b2ef7/summary?rt=4sXcuNICaU2liaSNEcQuUQ",

}

TY - CONF

T1 - Synthesis of fluorinated sterols and trojan horse inhibition of ergosterol biosynthesis in Trypanosoma brucei

AU - Leaver, David

PY - 2025

Y1 - 2025

N2 - The causative agent for Human African Trypanosomiasis (HAT) is Trypanosoma brucei and it is noted that this protozoan parasite is dependent on ergosterol for growth. 26-Fluorolanosterol (26FL) and 26-fluorocholesta-5,7,24-trienol (26-FCT) were observed to be irreversible (mechanism-based) inhibitors of the T. brucei sterol C24-methyltransferase (24-SMT). 24-SMT is an essential enzyme for T. brucei, however, this enzyme is not found in the human host, which makes inhibiting 24-SMT with small molecules an attractive therapeutic strategy. The synthesis of 26FL and 26-FCT will be discussed in addition to their ability to poison ergosterol biosynthesis in T. brucei.

AB - The causative agent for Human African Trypanosomiasis (HAT) is Trypanosoma brucei and it is noted that this protozoan parasite is dependent on ergosterol for growth. 26-Fluorolanosterol (26FL) and 26-fluorocholesta-5,7,24-trienol (26-FCT) were observed to be irreversible (mechanism-based) inhibitors of the T. brucei sterol C24-methyltransferase (24-SMT). 24-SMT is an essential enzyme for T. brucei, however, this enzyme is not found in the human host, which makes inhibiting 24-SMT with small molecules an attractive therapeutic strategy. The synthesis of 26FL and 26-FCT will be discussed in addition to their ability to poison ergosterol biosynthesis in T. brucei.

M3 - Presentation only

T2 - The 16th International Meeting on Biosynthesis, Function and Synthetic Biology of Isoprenoids

Y2 - 4 August 2025 through 8 August 2025

ER -

Synthesis of fluorinated sterols and trojan horse inhibition of ergosterol biosynthesis in Trypanosoma brucei

Abstract

Conference

Fingerprint

Research output

Fluorinated Sterols Are Suicide Inhibitors of Ergosterol Biosynthesis and Growth in Trypanosoma brucei

Cite this