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[摘要]：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 nonsmall cell human lung cancer cells (NCI-H460). The results were compared with digitoxin and its aglycone digitoxigenin. Three novel digitoxin monosaccharide analogues with beta-D-digitoxose, alpha-L-rhamnose, and alpha-L-amicetose sugar moieties showed excellent selectivity and activity. Further investigation revealed that digitoxin alpha-L-rhamnose and alpha-L-amicetose analogues displayed similar anti-proliferation 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. |
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