Antitumor activity of the marine natural product dibromophakellstatin in vitro

The pyrrole-imidazole alkaloid rac-dibromophakellstatin displayed selective antitumor activity in vitro when tested in 36 cell lines in a cell survival and proliferation assay. The ovarian cancer cell line OVXF 899L proved to be most sensitive (0.60 μM, IC 50), followed by the glioblastoma cell line CNXF 498NL (0.93 μM), the non-small lung cancer cell line LXF 529L (0.96 μM), and the uterus cancer cell line UXF 1138L (1.21 μM). The selectivity profile of rac-dibromophakellstatin may be indicative for a novel mechanism of action. Separation of the enantiomers on a chiral HPLC column revealed that only the naturally occurring (−)-dibromophakellstatin is antitumor active. Debromination of the pyrrole moiety leads to complete loss of activity.