Department of pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China.
Department of Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Eur J Med Chem. 2020 Feb 1;187:111959. doi: 10.1016/j.ejmech.2019.111959. Epub 2019 Dec 14.
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 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.
叶绿素 a 在光合作用中表现出优异的光敏活性。但其不稳定性限制了其作为光动力治疗中的光敏药物的应用。本研究合成了一系列新型叶绿素 a 降解产物原卟啉 IX 衍生物，并对其在光动力疗法中的肺癌进行了评价。这些化合物在 660-670nm 处具有较强的吸收，摩尔消光系数高，在 410-415nm 光激发下发射 660-675nm 的荧光。与原卟啉 IX 相比，它们的 ROS 产率都要高得多，而化合物 10 的 ROS 产率甚至高于[3-(1-己氧基乙基)]-原卟啉 IX（HPPH）。在体外观察到明显的光毒性，抑制效果呈光剂量和药物剂量依赖性。它们可以有效地抑制体内肺肿瘤的生长。其中，化合物 8 和 11 具有突出的光动力抗肿瘤作用，且无明显皮肤光毒性，因此可作为光动力治疗的新型候选药物。
