Umbelliferone Decorated Water‐soluble Zinc(II) Phthalocyanines – In Vitro Phototoxic Antimicrobial Anti‐cancer Agents

• Published in: Chemistry : a European journal Vol. 27; no. 59; pp. 14672 - 14680
• Main Authors: Sowa, Andrea, Höing, Alexander, Dobrindt, Ulrich, Knauer, Shirley K., Galstyan, Anzhela, Voskuhl, Jens
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 21.10.2021; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: Antiinfectives and antibacterials; antimicrobial; Antimicrobial activity; Antimicrobial agents; antitumor agents; Bacteria; Cancer; Chemistry; Chemistry, Multidisciplinary; coumarin; E coli; Gram-negative bacteria; Photodynamic therapy; Phototoxicity; phthalocyanines; Physical Sciences; Pyridines; Pyridinium; Science & Technology; Toxicity; Triethylene glycol; Tumors; Umbelliferone; Zinc; BEARING COUMARIN; antimicrobial; BACTERIA; ELECTROCHEMICAL PROPERTIES; coumarin; photodynamic therapy; PHOTOSENSITIZERS; PORPHYRIN; antitumor agents; phthalocyanines; OXYGEN; DERIVATIVES; METAL-FREE; AGGREGATION
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202102255

In this contribution we report on the synthesis, characterization and application of water‐soluble zinc(II) phthalocyanines, which are decorated with four or eight umbelliferone moieties for photodynamic therapy (PDT). These compounds are linked peripherally to zinc(II) phthalocyanine by a triethylene glycol linker attached to pyridines, leading to cationic pyridinium units, able to increase the water solubility of the system. Beside their photophysical properties they were analyzed concerning their cellular distribution in human hepatocyte carcinoma (HepG2) cells as well as their phototoxicity towards HepG2 cells, Gram‐positive (S. aureus strain 3150/12 and B. subtilis strain DB104) and Gram‐negative bacteria (E. coli strain UTI89 and E. coli strain Nissle 1917). At low light doses and concentrations, they exhibit superb antimicrobial activity against Gram‐positive bacteria as well as anti‐tumor activity against HepG2. They are even capable to inactivate Gram‐negative bacteria, whereas the dark toxicity remains low. These unique water‐soluble compounds can be regarded as all‐in‐one type photosensitizers with broad applications ranges in the future. Presented here are umbelliferone substituted water‐soluble zinc(II) phthalocyanines, which are able to inactivate efficiently Gram‐positive and Gram‐negative bacteria and are also active against HepG2 cancer cells. The compounds were investigated concerning their phototoxicity as well as their photophysical properties and their aggregation behavior.