THE SYNTHESIS, ANTILEUKEMIC ACTIVITY, AND CRYSTAL-STRUCTURES OF INDIRUBIN DERIVATIVES

In order to search for a new kind of antileukemic drug, we synthesized four indirubin derivatives, including indirubin monooxime (IM), indir ubin monooxime O-methyl ether (IMME), N-1-methylindirubin monooxime O- methyl ether (MIMME), and indirubin monooxime O-ethyl ether (IMEE). Th eir antileukemic activities in vivo and in vitro were tested; some of these compounds showed good activities. Their molecular and crystal st ructures were determined by an X-ray diffraction method. The results r evealed that all four indirubin derivatives are planar, and have a ten dency to form a big pi-system. The molecular structures also showed th at oximation of indirubin resulted in only a slight change in the anti leukemic activity. On the other hand, the amido moiety in the compound s may play an important role in the activity of the indirubin monooxim e derivatives. This conclusion was supported by the calculation result s of the electrostatic-potential (esp) derived charge distribution of the indirubin derivatives, which were obtained using an ab initio mole cular orbital of the basis set (3-21G), taking the electronic correlat ion into account at the MP2 level.