Magalhães Carla M, González-Berdullas Patricia, Duarte Diana, Correia Ana Salomé, Rodríguez-Borges José E, Vale Nuno, Esteves da Silva Joaquim C G, Pinto da Silva Luís
Chemistry Research Unit (CIQUP), Faculty of Sciences, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
Biomedicines. 2021 Sep 11;9(9):1199. doi: 10.3390/biomedicines9091199.
Photodynamic therapy (PDT) is an anticancer therapeutic modality with remarkable advantages over more conventional approaches. However, PDT is greatly limited by its dependence on external light sources. Given this, PDT would benefit from new systems capable of a light-free and intracellular photodynamic effect. Herein, we evaluated the heavy-atom effect as a strategy to provide anticancer activity to derivatives of coelenterazine, a chemiluminescent single-molecule widespread in marine organisms. Our results indicate that the use of the heavy-atom effect allows these molecules to generate readily available triplet states in a chemiluminescent reaction triggered by a cancer marker. Cytotoxicity assays in different cancer cell lines showed a heavy-atom-dependent anticancer activity, which increased in the substituent order of hydroxyl < chlorine < bromine. Furthermore, it was found that the magnitude of this anticancer activity is also dependent on the tumor type, being more relevant toward breast and prostate cancer. The compounds also showed moderate activity toward neuroblastoma, while showing limited activity toward colon cancer. In conclusion, the present results indicate that the application of the heavy-atom effect to marine coelenterazine could be a promising approach for the future development of new and optimized self-activating and tumor-selective sensitizers for light-free PDT.
光动力疗法（PDT）是一种抗癌治疗方式，与更传统的方法相比具有显著优势。然而，PDT因其对外部光源的依赖而受到极大限制。鉴于此，PDT将受益于能够实现无光照和细胞内光动力效应的新系统。在此，我们评估了重原子效应作为一种策略，为腔肠素衍生物提供抗癌活性，腔肠素是一种在海洋生物中广泛存在的化学发光单分子。我们的结果表明，使用重原子效应可使这些分子在由癌症标志物触发的化学发光反应中产生易于获得的三线态。在不同癌细胞系中的细胞毒性试验显示出重原子依赖性抗癌活性，其活性随取代基顺序羟基＜氯＜溴而增加。此外，发现这种抗癌活性的大小也取决于肿瘤类型，对乳腺癌和前列腺癌更具相关性。这些化合物对神经母细胞瘤也显示出适度活性，而对结肠癌显示出有限活性。总之，目前的结果表明，将重原子效应应用于海洋腔肠素可能是未来开发新型、优化的无光照PDT自激活和肿瘤选择性敏化剂的一种有前景的方法。
