Department of Biochemical Sciences, ‡Department of Pharmaceutical Chemistry and Drug Control, and §Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague , Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
J Med Chem. 2015 Feb 26;58(4):1736-49. doi: 10.1021/jm5014852. Epub 2015 Feb 4.
Novel zinc, magnesium, and metal-free octasubstituted phthalocyanine photosensitizers bearing [(triethylammonio)ethyl]sulfanyl substituents in the peripheral or nonperipheral positions were synthesized and investigated for their photophysical properties (ΦΔ value up to 0.91, λmax up to 750 nm) and photodynamic anticancer activity. The photodynamic treatment of 3T3, HeLa, SK-MEL-28, and HCT 116 cancer cells revealed that the magnesium complexes were not active (IC50 > 100 μM), whereas the IC50 values of the zinc complexes typically reached values in the submicromolar range with low toxicity in the dark (TC50 ≈ 1500 μM). The subcellular changes upon photodynamic treatment of the HeLa cells indicated that the studied photosensitizers induced damage primarily to the lysosomes, which was followed by a relocalization and damage to other organelles. The time-lapse morphological changes along with the flow cytometry and caspase activity measurements indicated a predominant involvement of necrosis-like cell death.
新型锌、镁和无金属的八取代酞菁光敏剂，在其外围或非外围位置带有[(三乙氨基)乙基]硫烷基取代基，它们的光物理性质（ΦΔ 值高达 0.91，λmax 高达 750nm）和光动力抗癌活性已被研究。对 3T3、HeLa、SK-MEL-28 和 HCT 116 癌细胞的光动力处理表明，镁配合物没有活性（IC50＞100μM），而锌配合物的 IC50 值通常达到亚微摩尔范围，在黑暗中毒性低（TC50≈1500μM）。HeLa 细胞经光动力处理后的亚细胞变化表明，所研究的光敏剂主要诱导溶酶体损伤，随后其他细胞器发生重定位和损伤。时间 lapse 形态变化以及流式细胞术和半胱氨酸天冬氨酸蛋白酶活性测定表明，坏死样细胞死亡占主导地位。
