title: 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.affiliation: Fushimi Pharmaceutical Co., Ltd, 1676 Nakazu-cho, Marugame, Kagawa 763-8605, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Asano
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
authors.forename: Amon
authors.initials: A
authors.lastname: Nagami
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fukumoto
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Yazama
authors.affiliation: Department of Pharmacognosy, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Porphyrin Lab, 1-2-35 Tsushimanishizaka, Kita-ku, Okayama 700-0086, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakata
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan. Electronic address: atai@pu-hiroshima.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tai
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin