Derivatives of 5‐Aminolevulinic Acid for Photodynamic Therapy: Enzymatic Conversion into Protoporphyrin
Derivatives of 5‐Aminolevulinic Acid for Photodynamic Therapy: Enzymatic Conversion into Protoporphyrin
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DOI：
10.1111/j.1751-1097.1998.tb05178.x
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发表时间：
1998-01
影响因子：
3.3
通讯作者：
J. Kloek;Willem Akkermans;G. B. Henegouwen
中科院分区：
文献类型：
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作者：
J. Kloek;Willem Akkermans;G. B. Henegouwen
近年来，5-氨基乙酰丙酸(ALA)已成为光动力疗法(PDT)的一种广泛应用的药物。在有核细胞中，丙氨酸被转化为内源性光敏剂原卟啉IX(PpIX)。ALA的一个主要缺点是生物利用度低。因此，必须给予大剂量的ALA，以达到临床上相关的PpIX水平。此外，由于ALA对组织的渗透性差，只能治疗位于表面的病变。产品地毯的概念可能会为这个问题提供一个可能的解决方案。本研究合成了丙氨酸前药。这些ALA前体药物被证明比ALA本身在细胞中导致更高的PPIX水平。在丙氨酸的一系列酯前体药中，丙氨酸戊酯的荧光强度最高。此外，还在裂解细胞中研究了这些衍生物的酶促转化为ALA和PPIX的反应。在这种情况下，烷基链较短的酯诱导的荧光最强。酶促前药转化产生的副产物醇类对实验没有影响。
In recent years, 5‐aminolevulinic acid (ALA) has become a widespread agent for photodynamic therapy (PDT). In nucleated cells, ALA is converted into the endogenous photosensitizer protoporphyrin IX (PpIX). A major drawback of ALA is its low bioavailability. As a result, high doses of ALA must be administered in order to reach clinically relevant levels of PpIX. Moreover, only superficially located lesions can be treated as a result of the poor penetration of ALA into tissues. A possible solution for this problem may be provided by the prod rug concept. In the present study, prodrugs of ALA have been synthesized. These ALA prodrugs are shown to result in higher PpIX levels in cells than does ALA itself. Of a range of ester prodrugs of ALA, the ALA‐pentyl ester elicits the highest fluorescence. Further‐more, the enzymatic conversion of the derivatives into ALA and PpIX has been studied in lysed cells. Under these circumstances, the esters with the shorter alkyl chains induce the highest fluorescence. The alcohols that arise as side products from enzymatic conversion of the prodrugs are shown to have no influence on the experiments.