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Issue 19, 2008
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Synthesis and biological evaluation of pyrophosphate mimics of thiamine pyrophosphate based on a triazole scaffold

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Abstract

Novel triazole-based pyrophosphate analogues of thiamine pyrophosphate (TPP) have been synthesised and tested for inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis. The thiazolium ring of thiamine was replaced by a triazole in an efficient two-step procedure. Pyrophosphorylation then gave extremely potent triazole inhibitors with KI values down to 20 pM, compared to a KD value of 0.35 μM for TPP. This triazole scaffold was used for further investigation and six analogues containing mimics of the pyrophosphate group were synthesised and tested for inhibition of PDC. Several effective analogues were found with KI values down to around 1 nM.

Graphical abstract: Synthesis and biological evaluation of pyrophosphate mimics of thiamine pyrophosphate based on a triazole scaffold

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Publication details

The article was received on 21 Apr 2008, accepted on 09 Jun 2008 and first published on 11 Jul 2008


Article type: Paper
DOI: 10.1039/B806580B
Citation: Org. Biomol. Chem., 2008,6, 3561-3572
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    Synthesis and biological evaluation of pyrophosphate mimics of thiamine pyrophosphate based on a triazole scaffold

    K. M. Erixon, C. L. Dabalos and F. J. Leeper, Org. Biomol. Chem., 2008, 6, 3561
    DOI: 10.1039/B806580B

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