The design and synthesis of novel chalcogenopyrylium dyes as agents for photodynamic therapy.

摘要

Photodynamic therapy (PDT) has recently been developed as a chemotherapeutic treatment for cancer, especially in the treatment of cancers such as lung, bladder, esophageal, gastric and colon cancers. PDT involves the selective delivery of light to a tumor mass through the use of catheters and fiber optic cables. PDT employs a drug, known as a photosensitizer, which upon activation by light undergoes a chemical reaction to produce a cytotoxic agent in the tumor cell. The ideal photosensitizers for PDT are materials that can localize in and around the tumor mass, and are non-toxic to normal cells. These dyes must be activated by light at wavelengths greater than 700nm, where penetration of light into tissue is optimal. Furthermore, these materials must be chemically efficient in producing the cytotoxic agent. Such an agent would allow the selective destruction of tumor tissue while leaving normal tissue intact.; The objective of this project is to design and synthesize novel clinical agents that will be useful as sensitizers for PDT. The sensitizers prepared are dyes closely related in structure to known cationic sensitizers already used in PDT, such as AA1. Although these dyes have been examined as photosensitizers for PDT, they absorb light of wavelengths that are too short for good tissue penetration, and are inefficient at producing the cytotoxic agents. Our goal is to provide heavy-atom analogues of these dyes, in particular, telluropyrylium and selenopyrylium analogues. The replacement of specific light atoms (i.e. oxygen, sulfur) of the known photosensitizers with heavy-atom (i.e. selenium, tellurium) analogues will have a two-fold effect. First, the use of telluropyrylium and selenopyrylium analogues should increase the wavelength of absorption of the photosensitizers. Second, telluropyrylium and selenopyrylium are more efficient at producing the cytotoxic agent singlet oxygen. These modifications will create photosensitizers for PDT.