COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents

Photodynamic therapy
(PDT) for cancer treatment has drawn increased
attention over the last decades. Herein, we introduce a novel family
of low-molecular-weight coumarins as potential PDT anticancer tools.
Through a systematic study with a library of 15 compounds, we have
established a detailed structure–activity relationship rationale,
which allowed the selection of three lead compounds exhibiting effective
in vitro anticancer activities upon visible-light irradiation in both
normoxia and hypoxia (phototherapeutic indexes up to 71) and minimal
toxicity toward normal cells. Acting as excellent theranostic agents
targeting mitochondria, the mechanism of action of the photosensitizers
has been investigated in detail in HeLa cells. The generation of cytotoxic
reactive oxygen species, which has been found to be a major contributor
of the coumarins’ phototoxicity, and the induction of apoptosis
and/or autophagy have been identified as the cell death modes triggered
after irradiation with low doses of visible light.