Synthesis of chemically diverse esters of 5- aminolevulinic acid for photodynamic therapy via the multicomponent Passerini reaction

GABRIEL F. GOLA; GABRIELA M. DI VENOSA; DANIEL A. S´AENZ; GUSTAVO H. CALVO; GABRIELA M. CABRERA; ADRIANA G. CASAS; JAVIER A. RAM´ıREZ

RSC Advances

Royal Society of Chemistry

Año: 2016

2046-2069

5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) isgaining increasing acceptance in medicine as an effective techniquefor the treatment of a variety of neoplastic lesions. Unfortunately, theefficacy of ALA-PDT is limited by the hydrophilic nature of the molecule,leading to poor penetration through malignant tissues. This factprompted the development of more lipophilic ALA derivatives, such asalkyl esters, although this strategy has potential drawbacks, mainlyassociated with the instability of ALA in solution. In this paper wedescribe a more versatile methodology for obtaining ALA esters basedon the three-component Passerini reaction, which involves mildconditions and a straightforward procedure, allowing efficientgeneration of chemically diverse libraries of ALA conjugates. Thepreliminary in vitro evaluation of the new designed compoundsallowed us to find a new promising conjugate with enhanced photodynamicproperties compared to ALA