Amino acid derivatives of pyropheophorbide-a ethers as photosensitizer: Synthesis and photodynamic activity

Ten new water-soluble amino acid conjugates of pyropheophorbide-a ethers 4a–4j were synthesized and investigated for their in vitro photodynamic antitumor activity. The results showed that all compounds exhibited higher phototoxicity and lower dark toxicity against three kinds of tumor cell lines than BPD-MA. In particular, the most phototoxic compound 4d and 4j individually showed IC50 values of 41 nmol/L and 33 nmol/L against HCT116 cell, which represented 7.8- and 9.7-fold increase of antitumor potency compared to BPD-MA, respectively, suggesting that they were promising photosensitizers for PDT applications because of their strong absorption at long wavelength (λmax > 650 nm), high phototoxicity, low dark cytotoxicity and good water-solubility.

Ten new water-soluble amino acid derivatives of pyropheophorbide-a ethers 4a–4j were designed and synthesized via 3 steps reaction using pyropheophorbide-a as key intermediate. All target compounds exhibited better phototoxicity than BPD-MA and the most phototoxic compound 4d and 4j individually showed IC50 values of 41 nmol/L and 33 nmol/L against HCT116 cell, which represented 7.8- and 9.7-fold increase of antitumor potency compared to BPD-MA.Figure optionsDownload as PowerPoint slide