Synthesis and in vitro photocytotoxicity of coumarin derivatives for one- and two-photon excited photodynamic therapy.

Triethylene glycol functionalized coumarin derivatives 1-5 were synthesized and investigated as photosensitizers for one- and two-photon excited photodynamic therapy (PDT). Their absorption, fluorescence, triplet-state quantum yields, and singlet oxygen quantum yields were found to be significantly related to the substituent at the 7-position of the coumarin ring. In vitro photocytotoxicity of these derivatives toward HepG2 cells was examined and compared with a clinical drug. In vitro generation of reactive oxygen species (ROS), cellular uptake, and intracellular distribution of these derivatives were also characterized to fully reveal their structure-property relationships. The results showed that derivative 5, with a two-photon absorption cross section value of 1556 GM, could be a powerful PDT agent for both superficial diseases and solid tumors.