Synthesis and Biological Analysis of Thiotetra(ethylene glycol) monomethyl Ether-Functionalized Porphyrazines: Cellular Uptake and Toxicity Studies.
Synthesis and Biological Analysis of Thiotetra(ethylene glycol) monomethyl Ether-Functionalized Porphyrazines: Cellular Uptake and Toxicity Studies.
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DOI：
10.1155/2008/391418
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Radosevich JA
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文献类型：
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作者：
Lee S;Vesper BJ;Zong H;Hammer ND;Elseth KM;Barrett AG;Hoffman BM;Radosevich JA
卟啉类化合物作为一类新型的卟啉衍生物，在肿瘤显像和治疗方面具有潜在的应用价值。我们在这里检查六个外围官能化的M[pz（）] pz与，3，或2（在反式构象）和M =或Zn，其中A是一个单元和B是一个稠合的-二异丙氧基苯并基团。在肿瘤和正常细胞中进行细胞活力/增殖测定和荧光显微镜检查。暗毒性研究表明，其中四种化合物在正常细胞和肿瘤细胞中都表现出毒性;一种在正常细胞和肿瘤细胞中都无毒，一种对正常细胞有选择性毒性。此外，三种pz显示出增强的光诱导毒性，在某些情况下，在比Photofrin中的反应所需的浓度低多达10倍的处理浓度下观察到这些效应。所有六种化合物都优先被肿瘤细胞吸收，这表明它们具有作为体外诊断剂和作为从病理标本中分离和纯化异常细胞的辅助剂的潜力。特别是，两个有前途的诊断候选人已被确定为这项工作的一部分。
The porphyrazines (pzs), a class of porphyrin analogues, are being investigated for their potential use as tumor imaging/therapeutic agents. We here examine six peripherally-functionalized M[pz()] pzs with , 3, or 2 (in a trans conformation) and M = or Zn, where A is an unit and B is a fused -diisopropyloxybenzo group. Cell viability/proliferation assays and fluorescence microscopy were carried out in both tumor and normal cells. Dark toxicity studies disclosed that four of the compounds exhibited toxicity in both normal and tumor cells; one was nontoxic in both normal and tumor cells, and one was selectively toxic to normal cells. Additionally, three of the pzs showed enhanced photo-induced toxicity with these effects in some cases being observed at treatment concentrations of up to ten-fold lower than that needed for a response in Photofrin. All six compounds were preferentially absorbed by tumor cells, suggesting that they have potential as in vitro diagnostic agents and as aids in the isolation and purification of aberrant cells from pathological specimens. In particular, two promising diagnostic candidates have been identified as part of this work.