Synthesis and biological evaluation of new chlorin derivatives as potential photosensitizers for photodynamic therapy.

Abstract

Three new water-soluble chlorin derivatives 3, 5 and 8 for potential use as photosensitizers in photodynamic therapy (PDT) for cancer were synthesized from photoprotoporphyrin IX dimethyl ester (1). The in vivo biodistribution and clearance of chlorin derivatives 3, 5 and 8 were investigated in tumor-bearing mice. Iminodiacetic acid derivative 8 showed the greatest tumor-selective accumulation among the new chlorin derivatives with maximum accumulation in tumor tissue at 3h after intravenous injection and rapid clearance from normal tissues within 24h after injection. The in vivo therapeutic efficacy of PDT using 8 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3h after injection of 8. Tumor growth was significantly inhibited by PDT using 8. These results indicate that iminodiacetic acid derivative 8 is useful as a new photosensitizer to overcome the disadvantages of photosensitizers that are currently in clinical use.

• Authors: Ryuji Asano, Amon Nagami, Yuki Fukumoto, Futoshi Yazama, Hideyuki Ito, Isao Sakata, Akihiro Tai
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 21 Issue 8 Pg. 2298-2304 (Apr 15 2013) ISSN: 1464-3391 [Electronic] England
• PMID: 23477944 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Photosensitizing Agents
• Porphyrins
• chlorin

Topics

• Animals
• Colonic Neoplasms
• Female
• Male
• Mice
• Mice, Inbred BALB C
• Photochemotherapy (methods)
• Photosensitizing Agents (pharmacokinetics, pharmacology)
• Porphyrins (chemical synthesis, chemistry, pharmacokinetics, pharmacology)