Diarylethene-based Pt(II) molecular switches: a novel approch to photoactivated chemotherapy
The photoactivation of metal complexes with potential anticancer activity is a hot topic of current research, as it may lead to the development of more selective and efficient drugs. Photoactivated chemotherapy (PACT) with coordination compounds is usually based on photochemical processes taking pla...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/400875 |
| Acceso en línea: | http://hdl.handle.net/10803/400875 |
| Access Level: | acceso abierto |
| Palabra clave: | Medicaments antineoplàstics Medicamentos antineoplásicos Antineoplastic agents Compostos organometàl·lics Compuestos organometálicos Organometallic compounds Fotoquímica Photochemistry Disseny de medicaments Diseño de medicamentos Drug design Ciències Experimentals i Matemàtiques 547 |
| Sumario: | The photoactivation of metal complexes with potential anticancer activity is a hot topic of current research, as it may lead to the development of more selective and efficient drugs. Photoactivated chemotherapy (PACT) with coordination compounds is usually based on photochemical processes taking place at the metal center. In contrast, an innovative ligand-mediated photoactivation approach that exploits the outstanding photochemical properties of diarylethenes has been developed in the present PhD thesis. Platinum(II) complexes from dithienylcyclopentene-based photoswitchable ligands have been designed and prepared. These systems exhibit two thermally stable, interconvertible photoisomeric forms, which present clearly distinct properties. The photochemical behavior of all ligands and metal complexes has been examined by means of 1H NMR and UV-Vis spectroscopies, and a number of crystal structures have been determined. Additionally, DFT calculations have been performed to analyze the effect produced by the attachment of different metal-binding units on the photochemical performance of the diarylethene synthon. Subsequently, the interaction of each photoisomer of the platinum(II) complexes with DNA has been thoroughly investigated using different techniques. These studies revealed that the light-triggered transformation of these systems effectively translates into different DNA binding modes and affinities, as desired for a photoactivatable drug. The antiproliferative activity of the complexes prepared has then been evaluated through various cell viability in vitro assays, which validated the potential applications of such diarylethene-based photoswitches for the development of a new class of photochemotherapeutic metallodrugs. |
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