The design and synthesis of glycol-functionalized porphyrins that contain one to four low molecular weight glycol chains that are linked via ether bonds to the meta-phenyl positions of meso-tetraphenylporphyrin and the comparison of fluorinated and nonfluorinated para derivatives are reported. The cellular uptake and photodynamic activity significantly depend on terminal groups of the glycol substituent. Hydroxy glycol porphyrins, in contrast with methoxy glycol porphyrins, show efficient intracellular transport and a high induction of apoptosis in tumor cell lines in vitro . Furthermore, the ethylene glycol chain at the meta position exhibits a superior efficacy that leads to the permanent ablation of human breast carcinoma (MDA-MB-231) in nude mice. In addition, fluorination enhanced the photosensitizing potential of para-phenyl derivatives. The analysis of the cell-death mechanism revealed that glycol-functionalized porphyrins represent novel nonmitochondrially localized photosensitizers that have a profound ability to induce apoptosis in tumor cells that act upstream of caspase activation. The strong interaction with a tumor marker (sialic acid) indicates the preferential association of these compounds with tumor cells.
- MeSH
- apoptóza účinky léků MeSH
- časové faktory MeSH
- experimentální nádory farmakoterapie MeSH
- financování organizované MeSH
- fotochemoterapie metody MeSH
- glykoly aplikace a dávkování farmakologie chemie MeSH
- injekce intravenózní MeSH
- lidé MeSH
- molekulární struktura MeSH
- molekulová hmotnost MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- porfyriny aplikace a dávkování farmakologie chemie MeSH
- protinádorové látky aplikace a dávkování farmakologie chemie MeSH
- průtoková cytometrie MeSH
- racionální návrh léčiv MeSH
- screeningové testy protinádorových léčiv MeSH
- stereoizomerie MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
