Synthesis and cytotoxicity of novel indirubin-5-carboxamides

Xinlai Cheng; Paul Rasqué; Sandra Vatter; Karl-Heinz Merz; Gerhard Eisenbrand

doi:10.1016/j.bmc.2010.04.066

Synthesis and cytotoxicity of novel indirubin-5-carboxamides

Bioorg Med Chem. 2010 Jun 15;18(12):4509-15. doi: 10.1016/j.bmc.2010.04.066. Epub 2010 Apr 28.

Authors

Xinlai Cheng¹, Paul Rasqué, Sandra Vatter, Karl-Heinz Merz, Gerhard Eisenbrand

Affiliation

¹ Department of Chemistry, Division of Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany.

PMID: 20488718
DOI: 10.1016/j.bmc.2010.04.066

Abstract

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.

MeSH terms

Amides / chemistry*
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / toxicity
Cell Line, Tumor
Humans
Indoles / chemical synthesis
Indoles / chemistry
Indoles / toxicity
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / toxicity
Protein Kinases / chemistry
Protein Kinases / metabolism
Solubility
Structure-Activity Relationship

Substances

Amides
Antineoplastic Agents
Indoles
Protein Kinase Inhibitors
Protein Kinases
indirubin