Natural and synthetic iminosugars as carbohydrate processing enzyme inhibitors for cancer therapy.
Iminosugars, featuring a basic nitrogen at the hetero atom position in carbohydrate rings, gain increasing interest in the search for novel approaches towards cancer drug development. This compound class is known as competitive inhibitors of carbohydrate manipulation enzymes, such as glycosidases, which are involved in tumor cell invasion and migration. Such enzymes are also responsible for the attachment of oligosaccharides to the cell surface of tumor cells, displayed as glycoproteins, glycolipids, and proteoglycans, which play an important role in malignant phenotype and tumor growth. Furthermore, cancer cells show an extremely active lysosomal system which is reflected by enhancement of glycoprotein turnover. Iminosugars were found to interact with glycosyl hydrolases responsible for this kind of action in cancer cells and thus open a new compound class in the research field of finding new anti-cancer activities. This review will focus on the role of iminosugars in cancer therapy and will give an overview of their properties.
Wrodnigg
Tanja M
TM
Glycogroup, Technische Universitaet Graz, Stremayrgasse 16, A-8010 Graz, Austria. t.wrodnigg@tugraz.at
Steiner
Andreas J
AJ
Ueberbacher
Bernhard J
BJ
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D050111:Imino Sugars / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism*
D000970:Antineoplastic Agents; D050111:Imino Sugars; D009844:Oligosaccharides; D006026:Glycoside Hydrolases