Synthesis of new photosensitizers with potential aplication in photodynamic therapy

Abstract

In recent years, the photodynamic therapy (PDT) has occupied a place of prominence among the non-invasive therapies developed. Based on a combination of a photosensitizer and light with an appropriate wavelength, PDT has enabled the cure of several diseases, especially some types of cancer. Therefore, in this project is proposed the synthesis of new photosensitizers with the objective of contributing to the possible development of compounds for use in PDT. In part of this work is proposed the synthesis of new chlorins through the Diels-Alder reaction between protoporphyrin IX dimethyl ester and maleic anhydride. The adducts obtained should be converted into ethyleneglycol derivatives by the one-pot addition of ethyleneglycol and subsequently transformed in the esters of the 5-aminolevulinic acid (ALA), among other sulphonated compounds such as sultone and taurin. For this approach, some synthetic models were conveniently prepared. The total synthesis of new phthalocyanines linked to ALA among other hydrophilic groups (ascorbic acid and sugar) is also proposed in order to obtain compounds adequately functionalized to present a better solubility and reduced aggregation. In both synthesis (chlorins and phthalocyanines), it is expected an increase of the characteristics of the photosensitizers, highlighting the possibility to prepare the compound-type photosensitizer-ALA and also the occurrence of synergistic effect between the ALA and the photosensitizer when applied in PDT. By developing new macrocycles and new synthetic methodologies, this project would constitute a key effort for the consolidation of a group devoted to the synthesis of porphyrins and phthalocyanines. Besides, it would give support to several research groups and would establish important collaborations at the Chemistry Department of the FFCLRP-USP, together with other institutions where PDT-related researches are also being developed. (AU)