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 microM, IC50), followed by the glioblastoma cell line CNXF 498NL (0.93 microM), the non-small lung cancer cell line LXF 529L (0.96 microM), and the uterus cancer cell line UXF 1138L (1.21 microM). 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.
Zöllinger
Michael
M
Ludwig Maximilian University, Department of Chemistry and Biochemistry, Butenandtstr. 5-13, 81377 Munich, Germany.
Kelter
Gerhard
G
Fiebig
Heinz-Herbert
HH
Lindel
Thomas
T
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007093:Imidazoles; D011758:Pyrroles; C104805:dibromophakellstatin