Synthesis and evaluation of novel chlorophyll a derivatives as potent photosensitizers for photodynamic therapy

摘要

Chlorophyll a exhibits excellent photosensitive activity in photosynthesis. The , unstability limited its application as photoensitizer drug in photodynamic therapy. Here a series of novel chlorophyll a degradation products pyropheophorbide-a derivatives were synthesized and evaluated for lung cancer in PDT. These compounds have strong absorption in 660-670 nm with high molar extinction coefficient and fluorescence emission in 660-675 nm upon excitation with 410-415 nm light They all have much 1 higher ROS yields than pyropheophorbide-a, and compound 10 was even higher than [3-(1-hexyloxyethyl)]-pyrophoeophorbide a (HPPH). Distinctive phototoxicity was observed in vitro and the inhibition effect was in light dose-dependent and drug dose-dependent style. They can effectively inhibit the growth of lung tumor in vivo. Among them, compound 8 and 11 have outstanding photodynamic anti-tumor effects without obvious skin photo-toxicity, so they can act as new drug candidates for photodynamic therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.