Modification of the Thioglycosyl-Naphthalimides as Potent and Selective Human O-GlcNAcase Inhibitors.

ABSTRACT: β-N-Acetylhexosaminidases are widely distributed exoglycosidases and have attracted significant attention due to their important roles in the field of pesticide and drug discovery. Remarkably, human O-GlcNAcase (hOGA) and human β-N-acetylhexosaminidase (HsHex) possess the same catalytic mechanism but play different physiological actions in vivo. In this Letter, we aim to improve the inhibitory potency and selectivity of previously reported thioglycosyl-naphthalimides against hOGA. The rational compound design led to the synthesis of 13r bearing a 4-piperidylnaphthalimide moiety as a highly potent hOGA inhibitor (K _i = 0.6 μM against hOGA) with good selectivity (K _i > 100 μM against HsHexB). Furthermore, to investigate the basi

SUBMITTER: Shen S 

PROVIDER: S-EPMC6295843 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature