Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors

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.

Cite this article as:

Simone I. Michela*, Mares J. Laura, Eveleens A. Clothilde, McCluskey Adam, Pappin B. Brighid , Kiefel J. Milton and Houston A. Todd *, Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors, Mini-Reviews in Medicinal Chemistry 2018; 18 (10) . https://dx.doi.org/10.2174/1389557517666171002161325