Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect
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 photody...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/9/1199 |
| _version_ | 1797520109744422912 |
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| author | Carla M. Magalhães Patricia González-Berdullas Diana Duarte Ana Salomé Correia José E. Rodríguez-Borges Nuno Vale Joaquim C. G. Esteves da Silva Luís Pinto da Silva |
| author_facet | Carla M. Magalhães Patricia González-Berdullas Diana Duarte Ana Salomé Correia José E. Rodríguez-Borges Nuno Vale Joaquim C. G. Esteves da Silva Luís Pinto da Silva |
| author_sort | Carla M. Magalhães |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T07:52:11Z |
| format | Article |
| id | doaj.art-4e212e9f6bbf460eb1af146d63325cbb |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T07:52:11Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-4e212e9f6bbf460eb1af146d63325cbb2023-11-22T12:08:28ZengMDPI AGBiomedicines2227-90592021-09-0199119910.3390/biomedicines9091199Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom EffectCarla M. Magalhães0Patricia González-Berdullas1Diana Duarte2Ana Salomé Correia3José E. Rodríguez-Borges4Nuno Vale5Joaquim C. G. Esteves da Silva6Luís Pinto da Silva7Chemistry Research Unit (CIQUP), Faculty of Sciences, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, PortugalChemistry Research Unit (CIQUP), Faculty of Sciences, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, PortugalOncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, PortugalOncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, PortugalLAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre 697, 4169-007 Porto, PortugalOncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, PortugalChemistry Research Unit (CIQUP), Faculty of Sciences, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, PortugalChemistry Research Unit (CIQUP), Faculty of Sciences, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, PortugalPhotodynamic 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.https://www.mdpi.com/2227-9059/9/9/1199photodynamic therapycancercoelenterazinechemiluminescenceheavy-atom effecttriplet chemiexcitation |
| spellingShingle | Carla M. Magalhães Patricia González-Berdullas Diana Duarte Ana Salomé Correia José E. Rodríguez-Borges Nuno Vale Joaquim C. G. Esteves da Silva Luís Pinto da Silva Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect Biomedicines photodynamic therapy cancer coelenterazine chemiluminescence heavy-atom effect triplet chemiexcitation |
| title | Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect |
| title_full | Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect |
| title_fullStr | Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect |
| title_full_unstemmed | Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect |
| title_short | Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect |
| title_sort | target oriented synthesis of marine coelenterazine derivatives with anticancer activity by applying the heavy atom effect |
| topic | photodynamic therapy cancer coelenterazine chemiluminescence heavy-atom effect triplet chemiexcitation |
| url | https://www.mdpi.com/2227-9059/9/9/1199 |
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