Journal of Medicinal Chemistry p. 6060 - 6076 (2017)
Update date:2022-08-15
Topics:
Ghazal, Basma
Machacek, Miloslav
Shalaby, Mona Abbas
Novakova, Veronika
Zimcik, Petr
Makhseed, Saad
High photodynamic activity was observed for hexadeca-cationic zinc, magnesium, and metal-free phthalocyanines (Pcs) and tetrapyrazinoporphyrazines with EC50 values as low as 5 nM (MCF-7 cells) for the best compound; this activity was several times better than that of clinically established photosensitizers verteporfin, temoporfin, S3AlOHPc, or protoporphyrin IX. This lead compound was characterized by low dark toxicity (TC50 = 369 μM), high efficiency against other cell lines (HCT 116 and HeLa), and possible activation by light above 680 nm. The excellent photodynamic activity resulted from the rigid spatial arrangement of the quaternized triazole moieties above and below the Pc core, as confirmed by X-ray crystallography. The triazole moieties thus formed two cationic donuts that protected the hydrophobic core against aggregation in water. The lysosomes were found to be the site of subcellular localization and were consequently the primary targets of photodynamic injury, resulting in predominantly necrotic cell death.
View MoreJiangsu Chiatai Qingjiang Pharmaceutical Co.,Ltd
Contact:+86-517-86283327
Address:9 North Hantai Road, Huaian, China
Contact:+86-0512-69209969
Address:Room 317,Lushan Road,Suzhou New District,Jiangsu Province,China.
Contact:+49-4101-3053-0
Address:Waldhofstrasse 14 ,25474 Ellerbek Germany
Contact:+86-574-87065746
Address:10th Floor, No.787 Baizhang East Road,
Zhongshan Haihong Medicine Co., Ltd.
Contact:86-0760-86925778 (0)18824993998
Address:A7 building,lianyuan road Torch Hi-tech Industrial Development Zone
Doi:10.1016/S0040-4039(00)88708-0
(1982)Doi:10.1002/jlac.198219821109
(1982)Doi:10.1021/jm00351a008
(1982)Doi:10.1248/cpb.31.333
(1983)Doi:10.1021/ja00345a062
(1983)Doi:10.1016/S0040-4020(01)87594-3
(1986)