Novel Five‐Membered Iminocyclitol Derivatives as Selective and Potent Glycosidase Inhibitors: New Structures for Antivirals and Osteoarthritis

Abstract

A novel 5-membered iminocyclitol derivative was found to be a potent and selective inhibitor of the glycoprotein-processing alpha-glucosidase with a Ki value of 53 nM. This compound was further derivatized to antiviral agents against Japanese encephalitis virus, dengue virus serotype 2 (DEN-2), human SARS coronavirus, and human beta-hexosaminidase (Ki = 2.6 nM), a new target for the development of osteoarthritis therapeutics.

Structure-activity relationships of bergenin derivatives effect on α-glucosidase inhibition

“…Therefore, we considered the linkage of benzoic acid and bergenin as well as benzoic acid moiety and bergenin moiety are critical factor of α-glucosidase inhibitory activity. These results accorded with previous reports that α-glucosidase was inhibited to a great extent when the compound contained a fused-aromatic ring and a heteroaromatic component 47 . From the structural-activity point of view, the presence of methoxy group at 3′-position on bergenin derivative moiety was potent factor of the α-glucosidase inhibitory activity.…”

Structure-Activity Relationships ofN-Cinnamoyl and Hydroxycinnamoyl Amides onα-Glucosidase Inhibition

“…This strong inhibition effects of compounds (14)(15)(16) are in accordance with literature data, concerning fivemembered iminocyclitol derivatives as potent glycosidase inhibitors [38].…”

Liposome-Mediated Delivery of Iminosugars Enhances Efficacy against Dengue Virus In Vivo

“…In trials as an anti-HIV therapy, administration of free drug did not sustain sufficiently high serum concentrations to achieve an antiviral effect (14). Since that time, iminosugars with improved in vitro potency (but concurrently greater cellular toxicity) have been developed (1,7,9,16,24,33). As a parallel approach to enhance NB-DNJ potency, liposome-mediated intracellular delivery of iminosugars shows great promise (30).…”