The synthesis, antileukemic activity, and crystal structures of indirubin derivatives

Article abstract of DOI:10.1246/bcsj.69.1621

In order to search for a new kind of antileukemic drug, we synthesized four indirubin derivatives, including indirubin monooxime (IM), indirubin monooxime O-methyl ether (IMME), N₁-methylindirubin monooxime O-methyl ether (MIMME), and indirubin monooxime O-ethyl ether (IMEE). Their antileukemic activities in vivo and in vitro were tested; some of these compounds showed good activities. Their molecular and crystal structures were determined by an X-ray diffraction method. The results revealed that all four indirubin derivatives are planar, and have a tendency to form a big π-system. The molecular structures also showed that oximation of indirubin resulted in only a slight change in the antileukemic activity. On the other hand, the amido moiety in the compounds may play an important role in the activity of the indirubin monooxime derivatives. This conclusion was supported by the calculation results of the electrostatic-potential (esp) derived charge distribution of the indirubin derivatives, which were obtained using an ab initio molecular orbital of the basis set (3-21G), taking the electronic correlation into account at the MP2 level.