Synthesis and cytotoxicity of novel indirubin-5-carboxamides.
Indirubins have been reported to act as potent inhibitors of protein kinases relevant to tumorigenesis and of tumor cell growth, but their development to antitumor drugs suffer from their poor water solubility. We synthesized a novel class of indirubin derivatives, indirubin-5-carboxamides, carrying amide substituents with basic centers. Quaternization or protonation of these alkylamino substituents provided indirubins with significantly improved solubility without loss of bioactivity.
Cheng
Xinlai
X
Department of Chemistry, Division of Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany.
Rasqué
Paul
P
Vatter
Sandra
S
Merz
Karl-Heinz
KH
Eisenbrand
Gerhard
G
D000577:Amides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship
D000577:Amides; D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C027185:indirubin