Syntheses and Photodynamic Activities of Novel Trisulfonated Zinc Phthalocyanine Derivatives

• Published in: Journal of medicinal chemistry 1997-11, Vol.40 (24), p.3897-3904
• Main Authors: Kudrevich, Svetlana, Brasseur, Nicole, La Madeleine, Carole, Gilbert, Sandra, van Lier, Johan E
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; General aspects; Indoles - chemical synthesis; Indoles - pharmacology; Male; Mammary Neoplasms, Experimental - drug therapy; Medical sciences; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Organometallic Compounds - chemical synthesis; Organometallic Compounds - pharmacology; Pharmacology. Drug treatments; Photochemotherapy; Pigments, Biological - chemical synthesis; Pigments, Biological - pharmacology; Radiation-Sensitizing Agents - chemical synthesis; Radiation-Sensitizing Agents - pharmacology; Sarcoma, Experimental - drug therapy; Sulfonic Acids - chemical synthesis; Sulfonic Acids - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm9702488

The synthesis of water-soluble, unsymmetrical, trisulfonated zinc phthalocyanines (ZnPcS3) as single products of the ring expansion of boron tri(4-sulfo)subphthalocyanine (SubPc) is reported. The novel, water-soluble trisulfo-SubPcB(OH) was prepared via hydrolysis of the tris(4-chlorosulfonyl)SubPcB(Br) which in turn was obtained from the condensation of 4-(chlorosulfonyl)phthalonitrile with BBr3 in 1-chlorobenzene. A number of ZnPcS3 analogues were prepared via the reaction of S3SubPcB(OH) with different diiminoisoindoline derivatives of increasing hydrophobicity. The reaction proceeds at relative low temperature with acceptable yields. Metalation of free base Pc's with zinc acetate dihydrate afforded the corresponding zinc complexes. Photodynamic activities were measured against the EMT-6 mouse mammary tumor cell line and compared to those of the known ZnPcS3 and ZnPcS4. Added (t-Bu)benzo and (t-Bu)naphtho groups increased the in vitro cell photoinactivation efficacy of the ZnPcS3, whereas addition of a fourth sulfobenzo or bulky diphenylpyrazino group decreased the activity of the parent molecule. The (t-Bu)naphthotrisulfobenzoporphyrazine induced the best in vivo photodynamic tumor control which, combined with its good solubility and broad absorption spectrum, renders this compound an interesting dye for photodynamic applications in medicine.