MEDI 400 |
| 5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl)-porphyrin (TPPF20) was used as a core platform to efficiently generate a variety of solution phase combinatorial libraries containing 21, 55, and 666 members. These porphyrin libraries have variety of substituents that includes carbohydrate, polar pyridyl, and alkane moieties. The choice of the substituents is made based up on the fact that sugar appended porphyrins are shown to be effective photodynamic agents in the induction of necrosis or apoptosis in several cancer cell lines. The pyridyl and alkyl chains are expected to provide appropriate amphiphathic characteristics to the porphyrin systems. These solution phase libraries are screened for binding to the MDA-MB-231 breast cancer cells by incubating the cells, washing away the unbound materials, and identifying the absorbed porphyrins in cell extracts by MALDI mass spectrometry. Porphyrin systems containing both thioglucose and pyridyl functions are effectively taken up by the cancer cells indicating that both glycosylation and amphipathicity are key properties in these selections. The compounds selected by the cancer cells were resynthesized directly. Fluorescence microscopy based cell binding assays of these winning compounds were made and were compared to the tetra (thioglucose) porphyrin derivative (TPPF16-Glu4) standard and confirm the selection criteria. |
|
Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Medicinal Chemistry |