Synthetic approaches to long-wavelength photosensitizers for photodynamic therapy and their preliminary biological activity

Abstract

ABSTRACT The chlorophyll-a degradation product, purpurin- 1 8 methyl ester (4), was converted into a series of new bactenochlorins (18)-(20). These stable bacteriochlorins have strong long-wavelength absorptions >800 nm, and were testedfor in vivo photosensitizing activity using the standard screening system of DBA/2 mice bearing iranspianted SMT/F tumors.In preliminary screening, among the photosensitizers tested so far, bacteriochlorins (19) and (20) have shown promisinganti-tumor activity. Preliminary attempts are described, using photo-Fenton chemistry, to synthesize photosensitizers whichwill display both Type-I and Type-I! photochemical behavior. 1. INTRODUCTION Sensitizers for photodynamic therapy (PDT) which absorb at long-wavelength long have become targets as so-called second generation photosensitizers.1 Such compounds are attractive to investigators for three main reasons, (i) transmission of low energy light through tissues is much more efficient than high energy light, which is efficiently scattered,(ii) the presence of significant molar extinction at long-wavelength (compared with Photofrmn® at 630 nm) might eventuallyenable lower doses to be used by the physician, with concomitant reduction in troublesome side effects such as residual skinphotosensitivity, and (iii) long-wavelength photosensitizers should facilitate the introduction of relatively inexpensive diodelasers for PDT.CO2H