Photodynamic therapy synthesis

S.V. Kudrevich, M.G. Galpem and J.E. van Lier (1994). Synthesis of Octacarboxytetra (2,3-pyrazino)porphyrazine novel water soluble photosensitizers for photodynamic therapy. Synthesis, 8, 779-781. 

There are, indeed, many biological implications that have been triggered by the advent of fullerenes. They range from potential inhibition of HIV-1 protease, synthesis of dmgs for photodynamic therapy and free radical scavenging (antioxidants), to participation in photo-induced DNA scission processes [156, 157, 158, 159, 160, 161, 162 and 163]. These examples unequivocally demonstrate the particular importance of water-soluble fullerenes and are summarized in a few excellent reviews [141, 1751. 

This report deals with the synthesis and biological evaluations concerning photodynamic therapy properties of porphyrinyl- and dihydroporphyrinyl-type sugar derivatives. The chosen conjugates have O- and >S-glycosidic moieties or ether and ester functions. 

Phenazines and their derivatives are known to be biologically significant molecules, especially in the field of photodynamic therapy. A recent example of the preparation of red shifted azine dyes potentially for photodynamic therapy was reported by Gloster and coworkers <99JHC25>. The synthesis of phenazine 171 from 170 was thought to take place through the following mechanism. 

Tedesco AC, Rotta JCG, Lunardi CN (2003) Synthesis, photophysical and photochemical aspects of phthalocyanines for photodynamic therapy. Curr Org Chem 7 187-196... 

The major emphasis of the research carried out to date in the expanded porphyrin area has been concerned with the synthesis and characterization of new systems. However, significant effort has been devoted recently to exploring the use of these macrocycles as sensitizers for photodynamic therapy (PDT) and as magnetic resonance imaging (MRI) contrast agents. These two applications serve as the most visible of several potential areas where expanded porphyrins could provide an improvement over existing technology. In this section, therefore, we review the work to date relative to both PDT and MRI and also comment briefly about the other areas of potential utility. 

Singlet oxygen is involved in many important chemical processes and photochemical applications, including photodynamic therapy (Special Topic 6.23), photocarcinogeneity (Special Topic 6.7) and phototoxicity (Special Topic 6.22), chemiluminescence (Section 5.6), atmospheric photochemistry (Special Topic 6.21), polymer degradation (Special Topic 6.13), photosynthesis1389 (Special Topic 6.25) or industrial organic synthesis (Special Topic 6.20). 

Perotti, C., Fukuda, H., DiVenosa, G., MacRobert, A. J., Batlle, A. and Casas, A, 2004, Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies. British Journal of Cancer. 90, 1660-1665. 

Total syntheses of six carboranyl-containing porphyrins bearing 33-44 wt% B for application in BNCT was described by Vicente et al. (2000). This class of compounds features carbon-carbon linkages between the carboranyl groups and the meso-phenyl substituents. The synthesis of tetra (4-carboranylphenyl) porphyrins and their zinc(ll) complexes also was presented (Vicente et al. 2002b). This type of nido-carboranylporphyrin is a promising sensitizer for both BNCT and the photodynamic therapy of tumors. Four more nido-carboranylporphyrins showed promise as boron carriers for the BNCT (Vicente et al. 2002a). 

The interaction of artificial metal ions/complexes with peptides/proteins [11], nucleic acids/DNA [12,13], enzymes [14], steroids [15] and carbohydrates [16] forms a bridge between natural and artificial macromolecular metal complexes. Biometal-organie chemistry concentrates on such complexes [17]. The reason for the increasing interest in this field lies in medical applications of metal complexes (cancer, photodynamic therapy of cancer, immunoassays, fluorescence markers, enantioselective catalysis, template orientated synthesis of peptides, etc.). Figure 2-4 presents an overview of metals in medicine [18]. Some examples are given below. 

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