Water-soluble cationic derivatives of indirubin, the active anticancer component from Indigo naturalis.
To overcome the problem of poor aqueous solubility and bioavailability of indirubin-3-oximes, the compounds were modified by attaching a quaternary ammonium group at the oxime moiety. Exploring the prodrug concept, an oxime ester with acetyl-l-carnitine was prepared, and the rate of its hydrolysis was investigated to assess its suitability for clinical administration. In addition, the cytotoxic potency of new stable oxime ethers with a choline moiety and their influence on the cell cycle were tested in human cancer cell lines.
University of Vienna, Institute of Inorganic Chemistry, Währinger Str. 42, A-1090 Vienna, Austria.
Werner
W
Ginzinger
Alexander
A
Egger
Gerhard
G
Mühlgassner
Vladimir B
VB
Arion
Michael A
MA
Jakupec
Markus
M
Galanski
Walter
W
Berger
Bernhard K
BK
Keppler
D000108:Acetylcarnitine / Q000138:chemical synthesis / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002412:Cations / Q000737:chemistry; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D007203:Indigo Carmine; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D010091:Oximes / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry*
D000970:Antineoplastic Agents; D002412:Cations; D007211:Indoles; D010091:Oximes; D014867:Water; D000108:Acetylcarnitine; D007203:Indigo Carmine; C027185:indirubin