Synthesis and In Vitro Biological Evaluation of Psoralen‐Linked Fullerenes

Photodynamic therapy (PDT) is a widely used medicinal treatment for the cancer therapy that utilizes the combination of a photosensitizer (PS) and light irradiation. In this study, we synthesized two novel C60 fullerene derivatives, compounds 1 and 2, with a psoralen moiety that can covalently bind to DNA molecules via cross‐linking to pyrimidine under photoirradiation. Along with several fullerene derivatives, the biological properties of several novel compounds have been evaluated. Compounds 1 and 2, which have been shown to induce the production of hydroxyl radicals using several ROS detecting reagents, induced DNA strand breaks with relatively weak activities in the in vitro detection system using a supercoiled plasmid. However, the psoralen‐bound fullerene with carboxyl groups (2) only showed genotoxicity in the genotoxicity assay system of the umu test. Compound 2 was also seen to have cytotoxic activities in several cancer cell lines at higher doses compared to water‐soluble fullerenes. Psoralen‐conjugated fullerenes were synthesized. Psoralen is a well‐known DNA‐binding molecule via the cross‐linking pathway with pyrimidine moiety under UVA conditions. Fullerene can damage DNA by ROS formation under UVA conditions. Combination of these properties of psoralen and fullerene were checked by DNA scission activity, ROS formation ability and genotoxicity using the bacterial detection system. One of synthesized compounds was also found to be cytotoxic to several cancer cell lines.