N-Benzylgalactonoamidines as potent β-galactosidase inhibitors

A series of N-benzylgalactonoamidines was synthesized to probe their inhibitory ability during the hydrolysis of o-nitrophenyl-β-d-galactopyranoside by β-galactosidase (Aspergillus oryzae). All compounds are characterized as potent competitive inhibitors with inhibition constants (Ki) in the low nanomolar range (12-48 nM). The structure of the inhibitors mimics the bond-lengthening during the hydrolysis and the aromatic aglycon of the substrate. The electronic nature of the substituent in p-position of the aglycon influences the overall inhibitory ability most when compared to the unsubstituted parent compound.