Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents.
Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents.
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DOI：
10.1016/j.bmcl.2014.12.018
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发表时间：
2015-02
影响因子：
2.7
通讯作者：
Chun-Feng Zhu;S. Battah;Xiaole Kong;B. Reeder;R. Hider;Tao Zhou
中科院分区：
文献类型：
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作者：
Chun-Feng Zhu;S. Battah;Xiaole Kong;B. Reeder;R. Hider;Tao Zhou
5-氨基乙酰丙酸(ALA)前体药作为天然光敏剂原卟啉IX(PpIX)的前体已广泛应用于光动力疗法(PDT)。这种疗法的主要缺点是，由于ALA的高亲水性，它很难被细胞吸收。为了提高PpIX的疗效和产率，合成了一系列3-羟基吡啶-4-酮(HPO)偶联的丙氨酸前药。药代动力学研究表明，某些ALA-HPO结合物在人乳腺腺癌细胞系(MDA-MB-468)中比ALA更有效地产生PPIX。光暴露后细胞内的卟啉荧光水平与细胞的光毒性有很好的相关性，提示ALA-HPO偶联物在光动力治疗中有潜在的应用前景。
5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect and induce higher yields of PpIX, a range of prodrugs of ALA conjugated to 3-hydroxypyridin-4-ones (HPO) were synthesized. Pharmacokinetic studies indicated that some of the ALA–HPO conjugates are more efficient than ALA for PpIX production in the human breast adenocarcinoma cell line (MDA-MB-468). The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, suggesting the potential application of the ALA–HPO conjugates in photodynamic therapy.