Design, synthesis and inhibition activity of a novel cyclic enediyne amino acid conjugates against MPtpA.
In course of studies towards the discovery of selective inhibitors of MPtpA, a novel cyclic endiyne malonamic acid has been designed and synthesized.  The synthesis involves a crucial intramolecular Knoevenagel reaction.  The compound displayed a reversible non-competitive inhibition against MPtpA with inhibition constant K(i) of 22.5 μM. The enediyne acts as a recognition framework in inducing the inhibition and not as a reactive functional moiety.  This was confirmed by comparing the inhibiting activity with that of the corresponding saturated cyclic non-enediyne analogue.