DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF PHOTO-ACTIVABLE COMPOUNDS AGAINST CANCER STEM CELLS
Azo benzene compounds are widely studied now a days because of their potential light properties. The change of conformation (cis-trans) of these compounds with different wavelengths irradiation opens the possibility of light control over drugs, improving its selectivity over space and time. Therefor...
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| Tipo de recurso: | otro |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/420857 |
| Acceso en línea: | http://hdl.handle.net/10261/420857 |
| Access Level: | acceso abierto |
| Palabra clave: | Azobenzene Cancer stem cells (CSCs) http://metadata.un.org/sdg/3 http://metadata.un.org/sdg/9 Ensure healthy lives and promote well-being for all at all ages Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation |
| Sumario: | Azo benzene compounds are widely studied now a days because of their potential light properties. The change of conformation (cis-trans) of these compounds with different wavelengths irradiation opens the possibility of light control over drugs, improving its selectivity over space and time. Therefore, the possibility of decreasing the side effects of drugs and hence the precise dosing increases the interest of azo benzene compounds on therapeutic applications. Cancer stem cells (CSCs) are known for being responsible of relapse and for its survival over different cancer treatments. It has been observed that CSCs use, among other metabolic routes, autophagy to survive the treatments of cancer eradication. Autophagy is a metabolic pathway by which molecules renew its cellular material, and its inhibition will lead to sever side effects. Photopharmacology, using azo benzene compounds, could be a solution of these side effects, and develop a new cancer treatment with selectivity on tumorous zones with the aim of CSCs eradication by autophagy inhibition. For this purpose, the kinase enzyme ULK1 could be a therapeutic target for its inhibition as it is a protein that regulates the metabolic pathway of autophagy. Docking calculations have been performed to predict and select the photoswitchable molecules with best cis-trans change of activity in the pocket of ULK1 protein. Once the photoswicthable inhibitors were selected, a new synthetic route has been developed for these aminopyrimidine azo benzene compounds, which will be used in the future for further synthesis of similar molecules. A photoswitchable compound has been synthesized and its photochemical properties characterised for further use in biological assays. Photocharacterization has descarted the compound because of its photo chemical properties are not matching the requirements for future biological tests. Another photoswitchable compound has been detected but could not be isolated on the last step of the synthesis, and based on the data recorded of the detection, it seemed to have good photochemical properties for further biological tests |
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