Synthesis and biological studies of 5-aminolevulinic acid-containing dendrimers for photodynamic therapy

Using a convergent growth approach, a series of novel 5-aminolevulinic acid (ALA)-containing dendrimers have been synthesized. In these molecules, ALA residues are attached to the periphery by ester linkages, with amide bonds connecting the dendrons. Three first-generation dendrimers, bearing either 6 or 9 ALA residues, were synthesized by attachment of a tris(Boc-protecte d ALA)containing wedge (1) to a di- or tripodent aromatic, or tripodent ali phatic core. Two second generation 18-ALA-containing dendrimers were also s ynthesized using a 3,3'-iminodipropionic acid spacer unit between wedge 1 a nd the aromatic core. These compounds differed only in the distance between the core and the linker unit. The Boc-protected dendrimers were deprotecte d using trifluoroacetic acid and isolated as their TFA salts. The potential of these ALA ester dendrimers as macromolecular prodrugs for photodynamic therapy has been demonstrated in the tumorigenic keratinocyte PAM 212 cell line.