New derivatives of 5-aminolevulinic acid for photodynamic therapy: chemical synthesis and porphyrin production in in vitro and in vivo biological systems.
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.
Godal
Aslak
A
PhotoCure ASA, Hoffsveien 48, 0377 Oslo, Norway. ag@photocure.no
Nilsen
Nils O
NO
Klaveness
Jo
J
Branden
Jon Erik
JE
Nesland
Jahn M
JM
Peng
Qian
Q
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D011166:Porphyrins / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D004952:Esters; D017319:Photosensitizing Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid