Synthesis and photodynamic activities of modified benzochlorin derivatives on nasopharyngeal carcinoma cells

Nasopharyngeal carcinoma (NPC), endemic in Southern China, is ranked as the fourth leading cause of cancer deaths in Hong Kong. In an effort to develop new PDT agents for cancer treatment, with a particular emphasis on the NPC, we have investigated the benzochlorin-type photosensitizers. The chromophore is functionalized with side chains containing polar and/or cationic groups. Synthetic methods have been developed for such purposes; e.g. 5-chlorosulfonyloctaethylbenzochlorin and 5-bromooctaethylbenzochlorin are used as versatile precursors for the preparation of ammonium and amidinium salts. Preliminary in vitro study of the photodynamic activity of the synthetic compounds indicated that the cationic benzochlorin derivatives display significant photocytotoxicity towards NPC cells.

[1]  Raymond Bonnett,et al.  Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy , 1995 .

[2]  D. Dolphin,et al.  Porphyrin-Based Photosensitizers for Use in Photodynamic Therapy , 1998 .

[3]  N. Day,et al.  HLA and nasopharyngeal carcinoma in chinese —A further study , 1983, International journal of cancer.

[4]  R. Keck,et al.  COPPER BENZOCHLORIN, A NOVEL PHOTOSENSITIZER FOR PHOTODYNAMIC THERAPY: EFFECTS ON A TRANSPLANTABLE UROTHELIAL TUMOR , 1993, Photochemistry and photobiology.

[5]  T. Dougherty,et al.  A simple and efficient approach for the synthesis of fluorinated and nonfluorinated octaethylporphyrin-based benzochlorins with variable lipophilicity, their in vivo tumor uptake, and the preliminary in vitro photosensitizing efficacy. , 2001, The Journal of organic chemistry.

[6]  Chi K. Chang,et al.  Photodynamic activities of sulfonamide derivatives of porphycene on nasopharyngeal carcinoma cells. , 2003, Journal of biomedical science.

[7]  D. Kessel.  SITES OF PHOTODAMAGE BY THE IMINIUM SALT OF A COPPER OCTAETHYLBENZOCHLORIN , 1993, Photochemistry and photobiology.

[8]  M. C. F. Tong,et al.  Preliminary results of photodynamic therapy for recurrent nasopharyngeal carcinoma , 2004, European Archives of Oto-Rhino-Laryngology.

[9]  Byron C. Robinson,et al.  Functionalized benzochlorins for PDT , 1996, Photonics West.

[10]  S. Buchwald,et al.  Rational Development of Practical Catalysts for Aromatic Carbon—Nitrogen Bond Formation , 1999 .

[11]  D. Kessel,et al.  Rapid Initiation of Apoptosis by Photodynamic Therapy , 1996, Photochemistry and photobiology.

[12]  Kevin M. Smith,et al.  Vilsmeier reactions of porphyrins and chlorins with 3-(dimethylamino)acrolein to give meso-(2-formylvinyl)porphyrins: new syntheses of benzochlorins, benzoisobacteriochlorins, and benzobacteriochlorins and reductive coupling of porphyrins and chlorins using low-valent titanium complexes , 1991 .

[13]  W. Henle,et al.  Epstein‐barr virus and human malignancies , 1974 .

[14]  K. Chan,et al.  Synthesis of beta-Mono-, Tetra-, and Octasubstituted Sterically Bulky Porphyrins via Suzuki Cross Coupling. , 1996, The Journal of organic chemistry.

[15]  B. Henderson,et al.  Occupational and other non‐dietary risk factors for nasopharyngeal carcinoma in Guangzhou, China , 1990, International journal of cancer.