New sensitizers for photodynamic therapy: controlled synthesis of purpurins and their effect on normal tissue.
New sensitizers for photodynamic therapy: controlled synthesis of purpurins and their effect on normal tissue.
复制标题
光动力疗法的新型敏化剂：红紫素的受控合成及其对正常组织的影响。
DOI：
10.1021/jm00124a029
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发表时间：
1989
影响因子：
7.3
通讯作者：
Selman,SH
中科院分区：
文献类型：
--
作者：
Morgan,AR;Rampersaud,A;Garbo,GM;Keck,RW;Selman,SH
红嘌呤是一类卟啉衍生物，对4-（5-硝基-2-呋喃基）-2-噻唑基甲酰胺（FANFT）诱导的大鼠膀胱肿瘤（AY-27）具有良好的细胞毒性。从原卟啉I和粪卟啉I合成红嘌呤具有高产率和高度的区域选择性。产物的形成可以合理化的救济方面的空间应变周围的红紫素大环。使用大鼠足垫模型的治疗性光剂量的效果表明，在治疗性敏化剂剂量下，正常组织损伤在可接受的范围内，特别是对于金属化purpurpurins.Photodynamic疗法（PDT）作为治疗选定的人类肿瘤的新方法引起了一些关注。该技术使用一种外源性光敏剂“定位”在肿瘤中。与来自激光的可见光（红色）相结合，产生光动力效应，导致肿瘤破坏。目前应用最广泛的PDT光敏剂是血卟啉衍生物（HpD）或其推定的活性成分Photofrin II。虽然在非对照临床试验中有一定的效果，但HpD和Photofrin II都是各种卟啉物质的混合物，其各自对总生物效应的贡献尚不清楚。此外，这些物质的最大吸收在630 nm处，在该区域中，光穿透
Purpurins are a class of porphyrin derivative that have been shown to have good in vivo cytotoxicity to iV-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) inducedrat bladder tumors (AY-27) implantedinto Fisher 344 rats. The synthesis of purpurins from etioporphyrin I and coproporphyrin I proceeds in high yieldand with a high degree of regioselectivity. Product formation can be rationalized in terms of relief of steric strain about the periphery of the purpurin macrocycle. The effect of therapeutic light doses using the rat footpad model suggests that, at therapeutic sensitizer doses, normal tissue damage is within acceptable limits, particularly for metalated purpurins.Photodynamic therapy (PDT) has drawn some attention as a new approach to the treatment of selected human neoplasms. The technique uses an exogenously adminis-tered photosensitizer that “localizes” in the neoplasm. In combination with visible (red) light from a laser, a pho-todynamic effect is generated that leads to tumor de-struction. Currently, the most widely used photosensitizer for PDT is hematoporphyrin derivative (HpD) or its pu-tative active component Photofrin II. 1 Although some-what effective in uncontrolled clinical trials, both HpD and Photofrin II are mixtures of various porphyrin species, each of whose contribution to the total biological effectremains unclear. In addition, the absorption maxima of these species are at 630 nm, a region in which light penetration