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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8658-8670
Number of pages13
JournalJournal of Medicinal Chemistry
Volume58
Issue number21
DOIs
Publication statusPublished - Nov 12 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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