Synthesis, photophysical properties, and biological evaluation of trans-bisthioglycosylated tetrakis(fluorophenyl)chlorin for photodynamic therapy

Shiho Hirohara, Chio Oka, Masayasu Totani, Makoto Obata, Junpei Yuasa, Hiromu Ito, Masato Tamura, Hirofumi Matsui, Kiyomi Kakiuchi, Tsuyoshi Kawai, Masashi Kawaichi, Masao Tanihara

研究成果: Contribution to journalArticle査読

19 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)8658-8670
ページ数13
ジャーナルJournal of Medicinal Chemistry
58
21
DOI
出版ステータス出版済み - 11 12 2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 創薬

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