title: N-Heteroarylmethyl-5-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid a novel scaffold for the design of uncompetitive α-glucosidase inhibitors.
abstract: The enzyme α-glucosidase has attracted interest owing to its involvement in the digestive process of carbohydrate, its role in intracellular glycoprotein trafficking, tumorigenesis and viral infection. In this study, several members of a new family of N-heteroarylmethyl substituted azasugars were synthesized and evaluated as α-glucosidase inhibitors. We systematically investigated the effect of different N-substituents as well as the role of hydroxyl and carboxylate moieties on the piperidine ring. The compounds N-heteroarylmethyl-5-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid emerged as potent α-glucosidase inhibitors. Unlike Acarbose and other clinically relevant α-glucosidase inhibitors, these compounds act through a reversible uncompetitive mechanism of inhibition which make them attractive candidates for drug development.
authors.affiliation: ISOF-CNR Dep. 'G. Ciamician', Bologna, Italy. sha.long2@unibo.it
authors.forename: Sha
authors.initials: S
authors.lastname: Long
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Stefani
authors.forename: Stefano
authors.initials: S
authors.lastname: Biondi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ghiselli
authors.forename: Mauro
authors.initials: M
authors.lastname: Panunzio
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D050111:Imino Sugars / Q000737:chemistry; D007700:Kinetics; D011485:Protein Binding; D013379:Substrate Specificity; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D050111:Imino Sugars; D000520:alpha-Glucosidases
keywords: 1,2,5,6-Tetrahydropyridine-3-carboxylic acid; Azasugars; Iminosugars; Uncompetitive enzymatic inhibition; α-Glucosidase inhibitors