期刊
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
卷 173, 期 -, 页码 606-617出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.jphotobiol.2017.06.036
关键词
Cationic porphyrins; Flexible arms; G-quadruplex DNA; Photocytotoxicity
资金
- Natural Science Foundation of Guangdong [2016A030313807]
- Medical Science and Technology Research Fund Project of Guangdong Province [A2015448]
- Foundation of Major Science and Technology Projects of Guangdong Province [2013A022100040]
- Outstanding Young Teachers' Foundation in Colleges and Universities of Guangdong Province
DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design.
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