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Literature summary for 2.4.1.83 extracted from

  • Smith, T.K.; Young, B.L.; Denton, H.; Hughes, D.L.; Wagner, G.K.
    First small molecular inhibitors of T. brucei dolicholphosphate mannose synthase (DPMS), a validated drug target in African sleeping sickness (2009), Bioorg. Med. Chem. Lett., 19, 1749-1752.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.4.1.83

Application

Application Comment Organism
drug development inhibition of DPMS is a promising strategy for the development of anti-trypanosomal agents. Thiazolidinones [(5Z)-5-[[4-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid, [(5Z)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid and [(5Z)-5-[(2-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid in particular are promising candidates for further development because of their respective activities against trypanosomal DPMS and GPI anchor biosynthesis Trypanosoma brucei

Cloned(Commentary)

Cloned (Comment) Organism
full-length DPMS expressed in Escherichia coli Trypanosoma brucei

Inhibitors

Inhibitors Comment Organism Structure
additional information DPMS inhibitors prevent the biosynthesis of glycosylphosphatidylinositol anchors, and possess trypanocidal activity against live trypanosomes Trypanosoma brucei
[(5Z)-4-oxo-5-(phenylmethylidene)-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 42% residual DPMS activity in the presence of 1 mM Trypanosoma brucei
[(5Z)-5-[(2-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 23% residual DPMS activity in the presence of 1 mM. Does not affect dolichyl D-mannosyl phosphate production in the cell-free system, but potently inhibits formation of mannosylated glycosylphosphatidylinositol intermediates Trypanosoma brucei
[(5Z)-5-[(3-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 90% residual DPMS activity in the presence of 1 mM Trypanosoma brucei
[(5Z)-5-[(4-chlorophenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 86% residual DPMS activity in the presence of 1 mM Trypanosoma brucei
[(5Z)-5-[(4-cyanophenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 73% residual DPMS activity in the presence of 1 mM Trypanosoma brucei
[(5Z)-5-[(4-ethynylphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 94% residual DPMS activity in the presence of 1 mM Trypanosoma brucei
[(5Z)-5-[(4-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 70% residual DPMS activity in the presence of 1 mM. Abolishes the formation of dolichyl D-mannosyl phosphate almost completely, and significantly reduces the formation of downstream glycosylphosphatidylinositol intermediates Trypanosoma brucei
[(5Z)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 20% residual DPMS activity in the presence of 1 mM. Abolishes the formation of dolichyl D-mannosyl phosphate almost completely, and significantly reduces the formation of downstream glycosylphosphatidylinositol intermediates Trypanosoma brucei
[(5Z)-5-[[3-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 23% residual DPMS activity in the presence of 1 mM Trypanosoma brucei
[(5Z)-5-[[4-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid 10% residual DPMS activity in the presence of 1 mM. Does not affect dolichyl D-mannosyl phosphate production in the cell-free system, but potently inhibits formation of mannosylated glycosylphosphatidylinositol intermediates Trypanosoma brucei

Organism

Organism UniProt Comment Textmining
Trypanosoma brucei
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GDP-mannose + dolichyl phosphate
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 Trypanosoma brucei GDP + dolichyl D-mannosyl phosphate
-
 ?
additional information glycosylphosphatidylinositol anchor biosynthesis Trypanosoma brucei ?
-
 ?

Synonyms

Synonyms Comment Organism
dolicholphosphate mannose synthase
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 Trypanosoma brucei
DPMS
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 Trypanosoma brucei