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Abstract：
Chlorin e6 is a well-known photosensitizer used in photodynamic diagnosis and therapy. A method for identifying and purifying a novel process-related impurity during the synthesis of chlorin e6 has been developed. Its structure was elucidated using NMR and HRMS. This new impurity is formed from chlorophyll b rather than chlorophyll a, which is the source of chlorin e6. The intermediates formed during chlorin e6 synthesis were monitored using HPLC-mass spectrometry. This new impurity was identified as rhodin g7 71-ethyl ester, the structure of which remains unknown to date. The cytotoxic effects of this novel compound in both dark and light conditions were studied against five cancer cell lines (HT29, MIA-PaCa-2, PANC-1, AsPC-1, and B16F10) and a normal cell line (RAW264.7) and compared to those of chlorin e6. Upon irradiation using a laser at 0.5 J/cm2, rhodin g7 71-ethyl ester demonstrated higher cytotoxicity (2-fold) compared to chlorin e6 in the majority of the cancer cell lines. Furthermore, this new compound exhibited higher dark cytotoxicity compared to chlorin e6. Studies on singlet oxygen generation, the accumulation in highly vascular liver tissue, and the production of reactive oxygen species in MIA-PaCa-2 cancer cells via rhodin g7 71-ethyl ester correspond to its higher cytotoxicity as a newly developed photosensitizer. Therefore, rhodin g7 71-ethyl ester could be employed as an alternative or complementary agent to chlorin e6 in the photodynamic therapy for treating cancer cells.
摘要：
Chloine6是用于光动力诊断和治疗的众所周知的光敏剂。已开发出一种在二氢氯化素e6合成过程中鉴定和纯化与工艺相关的新型杂质的方法。使用NMR和HRMS阐明其结构。这种新的杂质是由叶绿素b而不是叶绿素a形成的，它是氯元素e6的来源。使用HPLC-质谱法监测在二氢卟啉e6合成过程中形成的中间体。这种新的杂质被鉴定为rhoding771-乙酯，其结构至今未知。研究了这种新型化合物在黑暗和光照条件下对五种癌细胞系（HT29，MIA-PaCa-2，PANC-1，AsPC-1和B16F10）和正常细胞系（RAW264.7）的细胞毒性作用，并与氯蛋白e6进行了比较。在使用0.5J/cm2的激光照射后，在大多数癌细胞系中，与二氢氯化素e6相比，rhoding771-乙酯表现出更高的细胞毒性（2倍）。此外，这种新的化合物表现出更高的黑暗细胞毒性相比，二氢卟啉e6。研究单线态氧的产生，在高血管肝组织中的积累，并且通过rhoding771-乙酯在MIA-PaCa-2癌细胞中产生活性氧对应于其作为新开发的光敏剂的更高的细胞毒性。因此,rhoding771-乙酯可以在光动力疗法中用作二氢卟啉e6的替代或补充剂，用于治疗癌细胞。
