Shedding lights on the flexible-armed porphyrins: Human telomeric G4 DNA interaction and cell photocytotoxicity research

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2017-08, Vol.173, p.606-617
• Main Authors: Sun, Xiang-Yu, Zhao, Ping, Jin, Shu-fang, Liu, Min-Chao, Wang, Xia-hong, Huang, Yu-min, Cheng, Zhen-feng, Yan, Si-Qi, Li, Yan-Yu, Chen, Ya-Qing, Zhong, Yan-Mei
• Format: Article
• Language: English
• Subjects: A549 Cells; Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Binding; Binding Sites; Biological effects; Cancer; Carbon; Cationic porphyrins; Cell Cycle Checkpoints - drug effects; Cell Cycle Checkpoints - radiation effects; Cell Line, Tumor; Cells; Chains; Circular Dichroism; Coordination compounds; Crystallography; Cytotoxicity; Deoxyribonucleic acid; DNA; Drug development; Flexible arms; Function analysis; G-quadruplex DNA; G-Quadruplexes - drug effects; G-Quadruplexes - radiation effects; HeLa Cells; Human performance; Humans; Inhibition; Light; Microscopy, Fluorescence; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Molecular docking; Molecular Docking Simulation; Nucleic Acid Conformation; Photocytotoxicity; Polymorphism; Porphyrins; Porphyrins - chemistry; Porphyrins - metabolism; Porphyrins - toxicity; Shedding; Singlet Oxygen - analysis; Telomere - genetics; Tumor cell lines
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2017.06.036

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. [Display omitted] •New flexible-armed cationic porphyrin dyes were synthesized and characterized.•Carbon side chains influence the G-quadruplex binding, folding and stabilizing activities.•These porphyrin dyes inhibit cell proliferation under irradiation, with inducing apoptosis by ROS.