Dipartimento Farmacochimico, Tossicologico e Biologico, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
Bioorg Med Chem. 2010 Jul 1;18(13):4830-43. doi: 10.1016/j.bmc.2010.04.080. Epub 2010 Apr 29.
In the search for new photochemotherapeutic agents, a series of derivatives of the ring system pyrrolo[3,2-h]quinoline--bioisosters of the angular furocoumarin angelicin--were synthesized through a four-step synthetic approach, in reasonable overall yields. Eight of the synthesized derivatives showed a remarkable phototoxicity against a panel of four human tumor cell lines and a great dose UV-A dependence, reaching IC₅₀ values at submicromolar level. The mode of cellular death photoinduced by pyrrolo[3,2-h]quinolines was evaluated through a series of flow cytometric analysis and other tests were performed to clarify their mechanism of action.
在寻找新的光化学治疗药物的过程中，通过四步合成方法，合理地获得了一系列吡咯并[3,2-h]喹啉环系的衍生物——角型呋喃香豆素花椒毒素的生物等排物。合成的 8 种衍生物对一组 4 个人类肿瘤细胞系表现出显著的光毒性和对 UV-A 剂量的强烈依赖性，达到亚微摩尔级别的 IC₅₀ 值。通过一系列流式细胞分析评估吡咯并[3,2-h]喹啉诱导的细胞死亡模式，并进行了其他测试以阐明其作用机制。
