Departamento de Química Inorgánica, Universidad de Murcia and Institute for Bio-Health Research of Murcia (IMIB-Arrixaca), Campus de Espinardo, Murcia E-30071, Spain.
Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, IBUB, Universitat de Barcelona, Martí i Franqués 1-11, Barcelona E-08028, Spain.
J Med Chem. 2021 Dec 9;64(23):17209-17220. doi: 10.1021/acs.jmedchem.1c01254. Epub 2021 Nov 19.
Photodynamic therapy (PDT) for cancer treatment has drawn increased attention over the last decades. Herein, we introduce a novel family of low-molecular-weight coumarins as potential PDT anticancer tools. Through a systematic study with a library of 15 compounds, we have established a detailed structure-activity relationship rationale, which allowed the selection of three lead compounds exhibiting effective in vitro anticancer activities upon visible-light irradiation in both normoxia and hypoxia (phototherapeutic indexes up to 71) and minimal toxicity toward normal cells. Acting as excellent theranostic agents targeting mitochondria, the mechanism of action of the photosensitizers has been investigated in detail in HeLa cells. The generation of cytotoxic reactive oxygen species, which has been found to be a major contributor of the coumarins' phototoxicity, and the induction of apoptosis and/or autophagy have been identified as the cell death modes triggered after irradiation with low doses of visible light.
光动力疗法（PDT）在癌症治疗方面受到了越来越多的关注。在这里，我们介绍了一类新型的低分子量香豆素作为潜在的 PDT 抗癌工具。通过对 15 种化合物库的系统研究，我们建立了详细的构效关系原理，从中选择了三种具有有效体外抗癌活性的先导化合物，它们在常氧和缺氧条件下（光疗指数高达 71）经可见光照射后能发挥作用，且对正常细胞的毒性最小。这些光动力治疗剂作为针对线粒体的优秀治疗药物，其作用机制在 HeLa 细胞中得到了详细研究。研究发现，细胞毒性活性氧的产生是香豆素光毒性的主要原因，而在低剂量可见光照射后，细胞凋亡和/或自噬被认为是触发的细胞死亡模式。
