Synthesis and evaluation of novel fluorinated hematoporphyrin ether derivatives for photodynamic therapy

A photosensitizer with high phototoxicity, suitable amphipathy and low dark toxicity could play a pivotal role in photodynamic therapy (PDT). In this study, a facile and versatile approach was adopted to synthesize a series of novel fluorinated hematoporphyrin ether derivatives (I₁-I₅ and II₁-II₄), and the photodynamic activities of these compounds were studied. Compared to hematoporphyrin monomethyl ether (HMME), all PSs showed preferable photodynamic activity against A549 lung tumor cells. The longest visible absorption wavelength of these compounds was approximately 622 nm. Among them, II₃ revealed the highest singlet oxygen yield (0.0957 min^-1), the strongest phototoxicity (IC₅₀ = 1.24 μM), the lowest dark toxicity in vitro, and exhibited excellent anti-tumor effects in vivo. So compound II₃ could act as new drug candidate for photodynamic therapy.