meso-Tetra(pentafluorophenyl)porphyrin as an efficient platform for combinatorial synthesis and the selection of new photodynamic therapeutics using a cancer cell line.
The four para fluoro groups on 5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl)-porphyrin (TPPF20) are known to react with a variety of nucleophiles, but the reaction conditions for this substitution reaction depend on the nature of the nucleophiles, e.g. primary amines versus thiols. Glycosylated derivatives of this core porphyrin have been shown to be effective photodynamic agents in the induction of necrosis or apoptosis in several cancer cell lines. The present report demonstrates that TPPF20 can be used as a core platform to efficiently generate a variety of solution-phase combinatorial libraries. The focused combinatorial libraries have substituents that are chosen from a set of motifs known to bind biopolymers such as DNA, be taken up by cancer cells, or to render the compounds amphipathic. Incubation of a breast cancer cell line with these solution-phase libraries, followed by cell lyses and extraction, affords a selection assay. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry of the extracts allows identification of the molecules taken up by the cells. Cell binding assays of the winning compounds synthesized directly indicate that both glycosylation and amphipathicity are key properties since neither tetraglycosylated porphyrins nor those with four polar groups are selected to the same extent. In addition, photodynamic efficacy was evaluated.
Samaroo
Diana
D
Department of Chemistry and Biochemistry, Hunter College and the Graduate Center of the City University of New York, 695 Park Avenue, New York, New York 10065,USA.
Vinodu
Mikki
M
Chen
Xin
X
Drain
Charles Michael
CM
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D005260:Female; D006031:Glycosylation; D006801:Humans; D009336:Necrosis / Q000473:pathology; D010777:Photochemistry; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000138:chemical synthesis / Q000627:therapeutic use*; D013050:Spectrometry, Fluorescence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D005464:Fluorobenzenes; D005466:Fluorocarbons
D000970:Antineoplastic Agents; D011166:Porphyrins; C526738:meso-tetra(pentafluorophenyl)porphyrin; D005464:Fluorobenzenes; D005466:Fluorocarbons