[Photosensitizing anticancer tetrapyrroles: or how photophysics becomes a mechanism of action]

Abstract

The macrocyclic tetrapyrrole derivatives used for the treatment of certain solid tumors include porphyrins and their chlorine and bacteriochlorin derivatives. These are highly conjugated, rigid molecules characterized by a strong absorbance in the spectral domain from near ultra-violet to far red (350-750 nm). The combination of tetrapyrroles plus light is called dynamic phototherapy (DPT). This combination transforms the molecule to its triplet form which by deactivation generates free radicals and a singlet oxygen from molecular oxygen, causing tumor destruction. Tetrapyrroles are thus, with psoralens, used for the treatment of psoriasis. They are the only drugs whose mechanism of action results exclusively from their electronic and photophysical spectroscopic characteristics. This class of anticancer agents is usually free of any specific cytotoxic effect. We describe here the current elements linking structure and spectroscopy and observations leading to the design of compounds with strong tumor selectivity and optimal cytotoxic properties.