Biological Activity and Probable Mechanisms of Action of Derivatives of Tryptanthrin and Mostotrin Alkaloids.

The alkaloid tryptanthrin and its water-soluble derivative mostotrin exhibit high antimicrobial and antitumor activity. To develop more active and less toxic preparations, syntheses and testing of the biological activities of a number of new and/or little-studied analogs were performed. Some of them have been shown to have higher cytotoxicity against tumor and microbial cells than tryptanthrin and mostotrin. Thus, 8-fluorotryptanthrin effectively inhibits the proliferation of various tumor cell lines, namely: K-562/4, HCT-116 and HCT-116p53ko at lower concentrations than tryptanthrin, and 2,8-difluorostotrin exhibits a stronger antimicrobial effect against pathogenic bacteria S. aureus ATCC 29213 than mostotrin. It has been established that the antiproliferative properties of 8-fluorotryptanthrin and 8-fluoromostotrin are associated with their ability in nanomolar concentrations to inhibit the cell cycle of tumor cells at the stage of transition from the G phase to the S phase. The data obtained indicate the prospects for further in-depth studies of their antitumor properties.