Anti-neoplastic Activity of Cribrostatin 6 Derivatives
Cribrostatin 6 is a cytotoxic compound that inhibits the growth of murine leukemia P-388 cancer cells at 0.30 µM and also inhibits the growth of bacteria and fungi.3 Due to its high cytoxicity, derivatives of cribrostatin were synthesized and tested against four types of cell lines: U937 lymphoma, MCF-7 breast cancer, HeLa cervical cancer, and SK-MEL-5 melanoma cancer cells. Cell viability was determined with an MTS assay to determine the IC50s for all 12 compounds synthesized. The IC50 for cribrostatin 6 against U937 lymphoma cancer cells was determined to be 0.58 µM. From the 11 derivatives only one compound containing an azide was the more potent than cribrostatin 6 with an IC50 of 0.36 µM. Cell death and apoptosis was assessed using fluorescein-labeled annexin V and propidium iodide (PI) staining after U937 lymphoma cancer cells were treated for 12 hours. Cell cycle analysis and reactive oxygen species (ROS) production was determined. Cells were treated with 10 µM of cribrostatin 6 and derivative 8 and did not provide enough information to determine the phase of which cell growth was arrested. Future studies will consist of ROS experiment and cell cycle analysis.
School:
University of Illinois at Urbana-Champaign
Department:
Chemistry
Research Advisor:
Paul Hergenrother
Department of Research Advisor:
Chemistry
Year of Publication:
2008