Synthesis and Properties of Benzo[a]phenoxazinium Chalcogen Analogues as Novel Broad-Spectrum Antimicrobial Photosensitizers

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• 作者：James W. Foley ; Xiangzhi Song ; Tatiana N. Demidova ; Fatima Jilal ; Michael R. Hamblin
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：August 24, 2006
• 年：2006
• 卷：49
• 期：17
• 页码：5291 - 5299
• 全文大小：161K
• 年卷期：v.49,no.17(August 24, 2006)
• ISSN：1520-4804

文摘

The goal of this investigation was to develop improved photosensitizers for use as antimicrobial drugs inphotodynamic therapy of localized infections. Replacement of the oxygen atom in 5-(ethylamino)-9-diethylaminobenzo[a]phenoxazinium chloride (1) with sulfur and selenium afforded thiazinium andselenazinium analogues 2 and 3, respectively. All three dyes are water soluble, lipophilic, and red lightabsorbers. The relative photodynamic activities of the chalcogen series were evaluated against a panel ofprototypical pathogenic microorganisms: the Gram-positive Enterococcus faecalis, the Gram-negativeEscherichia coli, and the fungus Candida albicans. Selenium dye 3 was highly effective as a broad-spectrumantimicrobial photosensitizer with fluences of 4-32 J/cm² killing 2-5 more logs of all cell types thansulfur dye 2, which was slightly more effective than oxygen analogue 1. These data, taken with the findingsof uptake and retention studies, suggest that the superior activity of selenium derivative 3 can be attributedto its much higher triplet quantum yield.