期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 53, 期 21, 页码 7796-7803出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm1009555
关键词
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资金
- Spanish Ministerio de Ciencia e Innovacion [CTQ2007-67763-C03-01/BQU]
- U.S. NIH [R01A1050875]
- Generalitat de Catalunya (DURSI)
- Fons Social Europeu
- Bullock-Wellman Postdoctoral Fellowship
- Obra Social la Caixa
Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines, and phenothiazinium salts, with cationic charges at physiological pH values. However, derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse third degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log(10) reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J.cm(-2) of red light.
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