ISSN:
1573-9023
Keywords:
N-butyl-deoxynojirimycin
;
α-Glucosidase inhibitors
;
Anti-HIV prodrug
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Summary A novel class of compounds which are potent inhibitors of the posttranslational glycan trimming enzyme α-glucosidase I have been found to display anti-HIV activity. These compounds are iminosugar analogs ofd-glucose, with the oxygen in the ring replaced by a nitrogen, and were originally isolated from plants and microorganisms, although a considerable number of analogs have been synthesized during the past few years. One of these compounds,N-butyl-1-deoxynojirimycin (Bu-DNJ), is presently under evaluation in clinical trials for the control of HIV infections. Cumulative data, to date, suggest that compounds such asN-Bu-DNJ have a hierarchy of effects, with reduction in syncytia formation being the predominant feature, and are known to alter glycosylation of the HIV-1 envelope glycoproteins gp120 and gp41. Consequently, there are a number of different ways in which iminosugars may be exerting an antiviral effect. This paper discusses the basic properties of this class of compounds and the changes they effect in posttranslational processing of gp120 and gp41, as well as the synthesis and characterization of prodrug forms of Bu-DNJ (e.g.N-butyl-6-phospho-1-deoxynojirimycin), which do not inhibit intestinal disaccharidases and may be useful for eliminating the intestinal discomfort and diarrhea associated with administration of α-glucosidase inhibitors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02171663
Permalink