Gryshuk Amy, Chen Yihui, Goswami Lalit N, Pandey Suresh, Missert Joseph R, Ohulchanskyy Tymish, Potter William, Prasad Paras N, Oseroff Allan, Pandey Ravindra K
Chemistry Division, PDT Center, and Department of Dermatology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
J Med Chem. 2007 Apr 19;50(8):1754-67. doi: 10.1021/jm061036q. Epub 2007 Mar 20.
At similar lipophilicity, compared to the nonfluorinated purpurinimide 11, the corresponding fluorinated analog 8 with a trifluoromethyl substituent at the lower half (position-132) of the molecule showed enhanced photosensitizing efficacy. The structural parameters established in purpurinimides (lambdamax: 700 nm) were successfully translated to the bacteriopurpurin imide system 19 (lambdamax: 792 nm) and within both series, a monotonic relationship between the lipophilicity and the in vivo PDT activity was observed. For preparing water-soluble compounds, the photosensitizers 8 and 19 were converted into the corresponding aminobenzyl-diethylenetriamine pentaacetate conjugates 23 and 26. Acid treatment of purpurinimide 23 produced the corresponding water-soluble analog 24. Bacteriochlorin 26 under acidic or basic conditions mainly gave the decomposition products. At similar in vivo treatment conditions (C3H mice with RIF tumors and BALB-C mice with colon-26 tumors) the water-soluble purpurinimide 24 was found to be more effective than the methyl ester analog 8. These results suggest that besides overall lipophilicity the inherent charge of the photosensitizer also influences the PDT efficacy.
在相似的亲脂性条件下，与非氟化的紫红素亚胺11相比，分子下半部分（132位）带有三氟甲基取代基的相应氟化类似物8显示出增强的光敏效果。在紫红素亚胺（最大吸收波长：700 nm）中确定的结构参数成功转化到细菌紫红素亚胺体系19（最大吸收波长：792 nm）中，并且在这两个系列中，均观察到亲脂性与体内光动力疗法活性之间存在单调关系。为了制备水溶性化合物，将光敏剂8和19转化为相应的氨基苄基 - 二亚乙基三胺五乙酸缀合物23和26。对紫红素亚胺23进行酸处理得到相应的水溶性类似物24。细菌叶绿素26在酸性或碱性条件下主要产生分解产物。在相似的体内治疗条件下（患有RIF肿瘤的C3H小鼠和患有结肠26肿瘤的BALB - C小鼠），发现水溶性紫红素亚胺24比甲酯类似物8更有效。这些结果表明，除了整体亲脂性外，光敏剂的固有电荷也会影响光动力疗法的疗效。
