Title:Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors
Volume: 18
Issue: 10
Author(s): Michela I. Simone*, Laura J. Mares, Clothilde A. Eveleens, Adam McCluskey, Brighid B. Pappin, Milton J. Kiefel and Todd A. Houston*
Affiliation:
- Discipline of Chemistry, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW 2308,Australia
- Institute for Glycomics and School of Natural Sciences, Griffith University, Gold Coast Campus, Southport, QLD 4222,Australia
Keywords:
Cadmium, computational, copper, cyclophellitol, deoxynojirimycin, diabetes, electrophilic, epoxide, fucosidase,
galactosidase, glucocerebroside, glucosidase, glycal, homology, hydantocidin, iminosugar, lactam, lactone, mannosidase, metal
complex, modeling, molybdenum, natural product, palladium, salacinol, sialidase, silver, transition-state mimic, vanadium,
X-ray crystallography, zinc.
Abstract: Glycosidases have important anti-cancer, anti-viral and anti-diabetic properties. This review
covers the literature in the past 15 years since our initial review in this journal on “neutral” glycosidase
inhibitors lacking a basic nitrogen found in iminosugars and azasugars or inhibitors that are neutral by
virtue of being “charge-balanced” (zwitterionic). These structurally diverse inhibitors include lactones,
lactams, epoxides such as cyclophellitol, and sulfonium ion derivatives of the natural product salacinol.
Synthetic efforts toward cyclophillitol, salicinol and derivatives are also highlighted. Importantly, certain
metals can inhibit glycosidases and care must be taken to remove residual catalysts from synthetic
material to be tested against these enzymes.
