Potential Trypanocidal Activity of Glycerol Analogues.

Publisher: Wiley-VCH Verlag Country of Publication: Germany NLM ID: 101594811 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2191-1363 (Electronic) Linking ISSN: 21911363 NLM ISO Abbreviation: ChemistryOpen Subsets: MEDLINE

Original Publication: Weinheim : Wiley-VCH Verlag

Glycerol*/chemistry ; Glycerol*/pharmacology ; Trypanosoma brucei brucei*/drug effects ; Trypanocidal Agents*/pharmacology ; Trypanocidal Agents*/chemistry ; Trypanocidal Agents*/chemical synthesis ; Trypanocidal Agents*/toxicity

Glycerol, a versatile and ubiquitous compound, plays a vital role in a plethora of metabolic pathways in both prokaryotes and eukarotyes. Relatively few glycerol analogues have previously been explored for their use as glycerol kinase inhibitors, in addition to their therapeutic potential, however their use as (pro)-drugs in the context of parasitic diseases such as trypanosomiasis is unreported. The literature on glycerol metabolism and particular its synergic anti-profilation behaviour with salicylhydroxamic acid (SHAM) in Trypanosoma brucei is extensive. However, utiliation of glycerol analogues has not been explored as possible superior combinatory compounds. This report describes the synthesis of various glycerol analogues and their subsequent biochemical pheotypic analysis for their effect on lipid metabolism and their possible synergic activity with SHAM on Trypanosoma brucei. The glycerol analogues caused morphological changes;, including detached flagella, cytokinesis defects and 'big-eye' phenotype. All four compounds either matched or marginally increased the toxicity of SHAM when used in combination against Trypanosoma brucei. However, the compounds exhibited mostly an antagonistic relationship with SHAM rather than synergistic. This research highlights the potential of small molecule glycerol analogues for their combination use with SHAM for the treatment of parasitic disease, such as trypanosomiasis.
(© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

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Engineering and Physical Sciences Research Council, University of St. Andrews

Keywords: Trypanosma brucei; glycerol; lipids; salicylhydroxamic acid

PDC6A3C0OX (Glycerol)
0 (Trypanocidal Agents)

Date Created: 20240912 Date Completed: 20241209 Latest Revision: 20241211

20250114

PMC11625932

10.1002/open.202400094

39263751