COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents
| Autor: | Vicente Marchán, Joaquín Bonelli, Enrique Ortega-Forte, José Ruiz, Anna Rovira, Manel Bosch, Albert Gandioso |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Programmed cell death
medicine.medical_treatment Photodynamic therapy Antineoplastic Agents Apoptosis Article Medicaments antineoplàstics HeLa Structure-Activity Relationship Autofàgia Coumarins Drug Discovery Antineoplastic agents medicine Autophagy Humans Cells Cultured Cell Proliferation chemistry.chemical_classification Reactive oxygen species Photosensitizing Agents biology biology.organism_classification Mitochondria chemistry Mechanism of action Photochemotherapy Cancer research Molecular Medicine medicine.symptom Phototoxicity Reactive Oxygen Species Cumarines HeLa Cells |
| Zdroj: | Journal of Medicinal Chemistry Dipòsit Digital de la UB Universidad de Barcelona |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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