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

[ Vol. 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*   Pages 812 - 827 ( 16 )

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.

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.

Affiliation:

Discipline of Chemistry, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW 2308, Discipline of Chemistry, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW 2308, Discipline of Chemistry, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW 2308, Discipline of Chemistry, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW 2308, Institute for Glycomics and School of Natural Sciences, Griffith University, Gold Coast Campus, Southport, QLD 4222, Institute for Glycomics and School of Natural Sciences, Griffith University, Gold Coast Campus, Southport, QLD 4222, Institute for Glycomics and School of Natural Sciences, Griffith University, Gold Coast Campus, Southport, QLD 4222

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