Synthesis and evaluation of the α- D -/α-l-rhamnosyl and amicetosyl digitoxigenin oligomers as antitumor agents
A highly regio- and stereoselective asymmetric synthesis of rhamnosyl- and amicetosyl-digitoxigenin analogues has been established via palladium-catalyzed glycosylation followed by bis-/tris-dihydroxylation or bis-/tris-diimide reduction. The α-l-rhamnose and α-l-amicetose digitoxin monosaccharide analogues displayed stronger apoptosis inducing activity and cytotoxicity against nonsmall cell human lung cancer cells (NCI-H460) than its d-diastereomeric isomers in a sugar-chain length dependent manner.
Wang, Hua-Yu Leo,Rojanasakul, Yon,O'Doherty, George A.
Stereochemical survey of digitoxin monosaccharides
A stereochemically diverse array of monosaccharide analogues of the trisaccharide-based cardiac glycoside natural product digitoxin has been synthesized using a de novo asymmetric approach. The analogues were tested for cytotoxicity against the NCI panel of 60 human cancer cell lines and in more detail against nonsmall cell human lung cancer cells (NCI-H460). The results were compared with digitoxin and its aglycone digitoxigenin. Three novel digitoxin monosaccharide analogues with β-d-digitoxose, α-l-rhamnose, and α-l-amicetose sugar moieties showed excellent selectivity and activity. Further investigation revealed that digitoxin α-l-rhamnose and α-l-amicetose analogues displayed similar antiproliferation effects but with at least 5-fold greater potency in apoptosis induction than digitoxin against NCI-H460. This study demonstrates the ability to improve the digitoxin anticancer activity by modification of the stereochemistry and substitution of the carbohydrate moiety of this known cardiac drug.
Wang, Hua-Yu Leo,Xin, Wenjun,Zhou, Maoquan,Stueckle, Todd A.,Rojanasakul, Yon,O'Doherty, George A.
p. 73 - 78
(2011/04/17)
C5′-alkyl substitution effects on digitoxigenin α-l-glycoside cancer cytotoxicity
A highly regio- and stereoselective asymmetric synthesis of various C5′-alkyl side chains of rhamnosyl- and amicetosyl-digitoxigenin analogues has been established via palladium-catalyzed glycosylation with postglycosylated dihydroxylation or diimide reduction. The C5′-methyl group in both α-l-rhamnose and α-l-amicetose digitoxin analogues displayed a steric directed apoptosis induction and tumor growth inhibition against nonsmall cell human lung cancer cells (NCI-H460). The antitumor activity is significantly reduced when the steric hindrance is increased at the C5′-stereocenter.
Wang, Hua-Yu Leo,Wu, Bulan,Zhang, Qi,Kang, Sang-Woo,Rojanasakul, Yon,O'Doherty, George A.
p. 259 - 263
(2011/06/16)
3β-2',3'-Didesoxy-α,L-rhamnopyranoside von Cardenoliden
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Stache, Ulrich,Radscheit, Kurt,Haede, Werner,Fritsch, Werner
p. 560 - 561
(2007/10/02)
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