RESUMEN
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 G1 phase to the S phase. The data obtained indicate the prospects for further in-depth studies of their antitumor properties.
Asunto(s)
Alcaloides , Antineoplásicos , Staphylococcus aureus , Proliferación Celular , Antineoplásicos/farmacología , Alcaloides/farmacología , Línea Celular TumoralRESUMEN
Ten secondary metabolites including flavonoids (1-8), caffeic (9) and chlorogenic (10) acids were structurally identified from the extract of Sakhalin bilberry Vaccinium smallii leaves and studied in vitro as potential cancer-preventive agents. The results showed that compounds 1-10 inhibited EGF-induced neoplastic transformation of mouse JB6 Cl 41 P+ cells in soft agar with an inhibition concentration (INCC50) of 20-80 µm. Moreover, all these natural products were non-toxic against JB6 Cl 41 P+ cells up to a concentration of 200 µm.