Structure Optimization Of Indolecarbazole Derivatives

Indolecarbazoles are a class of natural products with potent biological activity, which attracted wide attention because of their structural diversity and biological activity. They can act on a variety of tumor-associated targets such as topoisomerase I TOPO I), protein kinase C, cell cycle protein (CDKs), and the checkpoint kinase and are regarded as valuable anti-tumor candidatesIn order to improve the water solublity of the indolocarbazoles, we synthesize21compounds by C ring opening, removal of the E ring, introduction of substituent group onto D ring, as well as the introduction of glycosylation fragment on the indole N-atom.We also tested the water solubility of target compounds and in vitro anti-tumor activity.The water solublity test results showed that the solubility of maleimides was increased significantly when a sugar residue was attached on the indole N-atom. However, introduction of sugar residues into the carbazoles does not improve the solubility in water at all.According to the cytotoxic activities of these compouds, the introduction of a sugar moiety onto NPCD did not affect much of their cytotoxic activities. Interestingly, NPCD showed distinct cell-cycle arrest profiles in BxPC3prostate cells and MCF-7breast cells, while NPCD glycosides shared similar cell cycle arrest profiles in MCF-7and BxPC3cells, which indicated that the subtle structure of the sugar moiety affected the underlying mechanism strongly.