Synthesis, Photophysical Properties, and Biological Evaluation of trans-Bisthioglycosylated Tetrakis(fluorophenyl)chlorin for Photodynamic Therapy
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- 作者：Shiho Hirohara ; Chio Oka ; Masayasu Totani ; Makoto Obata ; Junpei Yuasa ; Hiromu Ito ; Masato Tamura ; Hirofumi Matsui ; Kiyomi Kakiuchi ; Tsuyoshi Kawai ; Masashi Kawaichi ; Masao Tanihara
- 刊名：Journal of Medicinal Chemistry
- 出版年：2015
- 出版时间：November 12, 2015
- 年：2015
- 卷：58
- 期：21
- 页码：8658-8670
- 全文大小：608K
- ISSN：1520-4804
文摘
trans-Bisthioglycosylated tetrakis(fluorophenyl)chlorin (7) was designed as a powerful photodynamic therapy (PDT) photosensitizer based on the findings of our systematic studies. We show here that the trans-bisthioglycosylated structure of 7 enhanced its uptake by HeLa cells and that the chlorin ring of 7 increased the efficiency of reactive oxygen species generation under the standard condition of our photocytotoxicity test. The versatility of 7 in PDT treatment was established using weakly metastatic B16F1 melanoma cells, metastatic 4T1 breast cancer cells, the RGK-1 gastric carcinoma mucosal cell line, and three human glioblastoma cell lines (U87, U251, and T98G). The pharmacokinetics of 7 in mice bearing 4T1 breast cancer cells showed a high tumor-to-skin concentration ratio (approximately 60) at 24 h after intraperitoneal injection. The PDT efficacy of 7 in vivo was approximately 250-times higher than that of mono-l-aspartyl chlorin e6 (9) in mice bearing 4T1 breast cancer cells.