Photodynamic therapy (
PDT) has become a new treatment for several oncological and nononcological disorders. This procedure involves systemic or
topical administration of a lesion-localizing
photosensitizer or
prodrug, followed by irradiation with visible light to cause
singlet oxygen-induced damage to the target tissue. 5-aminolevulinic
acid (ALA) is an endogenous precursor for several photosensitizing
porphyrins formed by
heme biosynthesis, and has been studied for
PDT with promising results for some superficial diseases of the skin and hollow internal organs. Hydrophilic ALA has a limited ability to penetrate certain
biological barriers and has a relatively low selectivity for lesions. In addition, its ability to induce intracellular
porphyrins has been shown to be low compared to most
esters of ALA. This stimulated a search for lipophilic derivatives of ALA to overcome the shortcomings of ALA. Thirty-two new
esters of ALA were prepared and their ability to induce
porphyrin formation was assessed in the WiDr human
carcinoma cell line in vitro and in the normal skin of Balb/c nude mice in vivo. Branched-chain alkyl
esters and substituted benzyl
esters were found to be the most efficient
porphyrin precursors of the compounds studied.