The exogenous administration of 5-aminolaevulinic acid (ALA) is a relatively new approach in PDT since it is a naturally precursor of protoporphyrin IX (PPIX) which is an intermediate in 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 ALA can 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 (BCCs), using topical administration. However, ALAis a zwitterion at physiological pH and therefore has low lipid solubility, which limits its clinical application. More lipophilic ALA prodrugs are expected to cross cellular membranes more easily than ALA itself, resulting both in an enhanced depth of penetration and 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 photosensitiser levels both in vivo and in vitro.In this work, the synthetic strategy of multicomponent reactions (Passerini and the Ugi reactions ) to achieve new ALA prodrugs, and screening of the new compounds as potential pro-photosensitizers for PDT of cancer cell lines of different tissues will be shown. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/241nm/uploads/70262_figure.jpg' alt='' />

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

248th National Meeting (2014)

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