Synthesis and biological evaluation of nonionic substrate mimics of UDP-Galp as candidate inhibitors of UDP galactopyranose mutase (UGM).

Abstract The synthesis of 1-[5- O -(α- d -galactopyranosyl)- d -glucityl]pyrimidine-2,4(3 H )-dione and 1-[(5- O -(β- d -galactopyranosyl)- d -glucityl]pyrimidine-2,4(3 H )-dione as non-ionic substrate mimics of UDP-Gal p are described. UDP-Gal p is a precursor of Gal f , which is a primary component of the cell-wall glycans of several microorganisms. The interconversion of UDP-Gal p and UDP-Gal f is catalyzed by UDP galactopyranose mutase (UGM); its inhibition comprises a mode of compromising the microorganisms. The nonionic polyhydroxylated chain was intended to mimic the ionic pyrophosphate group and the ribose moiety in UDP-Gal p and increase the bioavailabilities of the candidate inhibitors. Inhibition assays with UGM of Mycobacterium tuberculosis showed only weak inhibition of the enzyme by these compounds.