Bioorganic & Medicinal Chemistry Letters 2007-01-01

Intermediate analogue inhibitors of mandelate racemase: N-Hydroxyformanilide and cupferron.

Jennifer R Bourque, Rodney K M Burley, Stephen L Bearne

Index: Bioorg. Med. Chem. Lett. 17 , 105-8, (2007)

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Abstract

Mandelate racemase (MR) catalyzes the 1,1-proton transfer that interconverts the enantiomers of mandelate. The transition state/intermediate analogues N-hydroxyformanilide (K(i)=2.79+/-0.19 microM) and cupferron (K(i)=2.67+/-0.09 microM) are identified as potent competitive inhibitors of MR. The pH-pK(i) profile indicates that MR can bind either the protonated or deprotonated forms of N-hydroxyformanilide, with a 10-fold greater affinity for the latter form.