title: A Direct Comparison of the Anticancer Activities of Digitoxin MeON-Neoglycosides and O-Glycosides: Oligosaccharide Chain Length-Dependent Induction of Caspase-9-Mediated Apoptosis.
abstract: Digitoxin is a cardiac glycoside currently being investigated for potential use in oncology. While a number of structure-activity relationship studies have been conducted, an investigation of anticancer activity as a function of oligosaccharide chain length has not yet been performed. We generated mono-, di-, and tri-O-digitoxoside derivatives of digitoxin and compared their activity to the corresponding MeON-neoglycosides. Both classes of cardenolide derivatives display comparable oligosaccharide chain length-dependent cytotoxicity toward human cancer cell lines. Further investigation revealed that both classes of compounds induce caspase-9-mediated apoptosis in non-small cell lung cancer cells (NCI-H460). Since O-glycosides and MeON-neoglycosides share a similar mode of action, the convenience of MeON-neoglycosylation could be exploited in future SAR work to rapidly survey large numbers of carbohydrates to prioritize selected O-glycoside candidates for traditional synthesis.
authors.affiliation: Department of Pharmaceutical Sciences, Hampton University, Hampton, VA 23668.
authors.forename: Anand Krishnan V
authors.initials: AK
authors.lastname: Iyer
authors.forename: Maoquan
authors.initials: M
authors.lastname: Zhou
authors.forename: Neelam
authors.initials: N
authors.lastname: Azad
authors.forename: Hosam
authors.initials: H
authors.lastname: Elbaz
authors.forename: Leo
authors.initials: L
authors.lastname: Wang
authors.forename: Derek K
authors.initials: DK
authors.lastname: Rogalsky
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
authors.forename: George A
authors.initials: GA
authors.lastname: O'Doherty
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Langenhan