Design and synthesis of novel water-soluble amino acid derivatives of chlorin p6 ethers as photosensitizer

Abstract Eight new water-soluble amino acid conjugates 6a - h of chlorin p 6 ethers ( 5a - d ) were synthesized and preliminarily investigated for their in vitro PDT antitumor activity and structure-activity relationship (SAR). The results showed that all compounds exhibited much higher phototoxicity against tumor cells than talaporfin. SAR analysis indicated that PDT antitumor effect enhanced with the increase of carbon chain length of alkoxyl ether bonds at 3 1 -position, and l -aspartic acid was superior to l -glutamic acid. In particular, the IC 50 values of most phototoxic compound 6d were 0.20 μmol/L against A549 cell and 0.41 μmol/L against B16-F10 cell, which individually represented 31- and 24-fold increase of antitumor potency compared to talaporfin, suggesting that it was a promising candidate photosensitizer (PS) for PDT applications due to its strong absorption at long wavelength, high phototoxicity, low dark cytotoxicity and good water-solubility.