School of Chemistry and Chemical Engineering, Key Laboratory of Functional Molecular Engineering of Guangdong Province, South China University of Technology, Guangzhou 510641, China.
Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou 510091, China.
Bioorg Chem. 2022 Dec;129:106177. doi: 10.1016/j.bioorg.2022.106177. Epub 2022 Sep 27.
Two new trimethoxyl AB triaryl corroles 10-(2,4,6-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)- corrole (1) and 10-(3,4,5-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)-corrole (2) and their gallium(III) and phosphorus(V) (1-Ga, 1-P, 2-Ga and 2-P) complexes had been prepared and well characterized by UV-vis, NMR and HR-MS. Among all compounds, 2-Ga, 1-P and 2-P showed excellent in vivo photodynamic activity against the MDA-MB-231, A549, Hela and HepG2 cell lines upon light irradiation at 625 nm. And 2-P even exhibited higher phototoxicity than the clinical photosensitizer temoporfin. Also, 2-P exhibited the highest singlet oxygen quantum yield and photostability. The preliminary investigation revealed that 2-P could be rapidly absorbed by tumor cells and mainly located in the cytoplasm. After photodynamic therapy (PDT) treatment with 2-P, mitochondrial membrane potential destruction, intracellular ROS level increasing and nuclear fragmentation of cancer cells could be observed. Cell cycle analysis demonstrated that the 2-P PDT may cause tumor cell arrest at sub-G1 stage and induce early and late apoptosis of cells. These results suggest that 2-P is a promising candidate as a photosensitizer for photodynamic therapy.
两个新的三甲氧基 AB 三芳基卟啉 10-(2,4,6-三甲氧基苯基)-5,15-双(五氟苯基)卟啉(1)和 10-(3,4,5-三甲氧基苯基)-5,15-双(五氟苯基)卟啉(2)及其镓(III)和磷(V)(1-Ga、1-P、2-Ga 和 2-P)配合物已经通过 UV-vis、NMR 和 HR-MS 进行了制备和充分表征。在所有化合物中,2-Ga、1-P 和 2-P 在 625nm 光照射下对 MDA-MB-231、A549、Hela 和 HepG2 细胞系具有优异的体内光动力活性。而且,2-P 甚至表现出比临床光增敏剂卟啉高出的光毒性。此外,2-P 还表现出最高的单线态氧量子产率和光稳定性。初步研究表明,2-P 可以被肿瘤细胞迅速吸收,主要位于细胞质中。在 2-P 的光动力治疗(PDT)治疗后,可以观察到线粒体膜电位破坏、细胞内 ROS 水平增加和癌细胞核碎裂。细胞周期分析表明,2-P PDT 可能导致肿瘤细胞停留在亚 G1 期,并诱导细胞的早期和晚期凋亡。这些结果表明,2-P 是一种很有前途的光动力治疗光敏剂候选物。