Multicomponent synthesis and in vitro screening of new prodrug derivatives of 5- aminolaevulinic acid for Photodynamic Therapy (PDT)

GOLA, J; SÁENZ D.; DI VENOSA G; CASAS, A.; GALAGOVSKY, L.; RAMÍREZ, J.

San Francisco

Congreso; 248th American Chemical Society National Meeting; 2014

American Chemical Society

The exogenous administration of 5-aminolaevulinic acid (ALA) is a relatively newapproach in PDT since it is a naturally precursor of protoporphyrin IX (PPIX) which is an intermediatein the haem biosynthetic pathway. PDT treatment is carried out using red light to activate the PPIX,resulting in the generation of cytotoxic reactive oxygen species. The exogenous administration of ALAcan induce significant intracellular levels of PPIX, which is an effective photosensitiser.At present, the main clinical PDT application of ALA is the treatment of basal cell carcinomas (BC C s),using topical administration. However, ALAis a zwitterion at physiological pH and therefore has lowlipid solubility, which limits its clinical application. More lipophilic ALA prodrugs are expected to crosscellular membranes more easily than ALA itself, resulting both in an enhanced depth of penetrationand a shorter topical application time. It has been reported that long chain ALA esters are taken up,desterified, and converted into PPIX with higher efficiency than ALA, leading to higher photosensitiserlevels both in vivo and in vitro.In this work, the synthetic strategy of multicomponent reactions (Passerini and the Ugi reactions ) toachieve new ALA prodrugs, and screening of the new compounds as potential pro-photosensitizers forPDT of cancer cell lines of different tissues will be shown.