Three derivatives of chlorin e6 (1–3) were synthesized by introduction of maleimide, cysteine and glutathione at C-13 carboxyl of the chlorin scaffold. The evaluation of their PDT effects showed that compound 1, the derivative with a maleimide group, exhibited more potent photocytotoxicity against HepG2 cells (IC50 3.2 μM) than 2 (IC50 6.7 μM) and 3 (IC50 10.2 μM), although the cellular uptake of 1 was slightly lower than that of 2 and 3. The high PDT effect of 1 was found to be in agreement with the high level of intracellular singlet oxygen. Further investigation of the mechanism revealed that 1 can significantly lower the GSH level in HepG2 cells due to the addiction reaction of maleimide and GSH, thus resulting in the reduction of ROS scavenging and the enhancement of cellular oxidative stress. This approach to improve PDT effects of photosensitizers by means of interfering with the cellular redox system and enhancing cellular oxidative stress offers a new strategy for development of photosensitizers in cancer therapy.

中文翻译：

---

用马来酰亚胺衍生二氢卟吩 e6 增强其在 HepG2 细胞中的光动力功效

二氢卟酚 e6 的三种衍生物 (1–3) 是通过在二氢卟酚支架的 C-13 羧基处引入马来酰亚胺、半胱氨酸和谷胱甘肽来合成的。对它们的 PDT 效果的评估表明，化合物1，具有马来酰亚胺基团的衍生物，对 HepG2 细胞表现出更强的光细胞毒性（IC503.2μM) 比2（我知道了506.7μM) 和3（我知道了5010.2μM），虽然细胞摄取1略低于2和3. 高PDT效应1发现与高水平的细胞内单线态氧一致。对该机制的进一步研究表明，1由于马来酰亚胺和 GSH 的成瘾反应，可显着降低 HepG2 细胞中的 GSH 水平，从而导致 ROS 清除减少和细胞氧化应激增强。这种通过干扰细胞氧化还原系统和增强细胞氧化应激来改善光敏剂PDT效果的方法为癌症治疗中光敏剂的开发提供了新的策略。