Design and development of hybrid se-compounds as multi-target and bioactive derivatives
- Autores: Cristina Moral Turón
- Directores de la Tesis: Arun Sharma (dir. tes.), María del Carmen Sanmartín Grijalba (dir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2025
- Idioma: inglés
- Tribunal Calificador de la Tesis: Daniel Plano Amatriain (presid.), Muhammad Raza (secret.), Enrique Domínguez Álvarez (voc.)
- Programa de doctorado: Programa de Doctorado en Medicamentos y Salud por la Universidad de Navarra
- Calificación: Sobresaliente Cum Laude
- Materias:
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- Resumen
The purpose of the present Ph. D. project entitled DESIGN AND DEVELOPMENT OF HYBRID SE-COMPOUNDS AS MULTI-TARGET AND BIOACTIVE DERIVATIVES was the development of suitable novel therapeutic agents by incorporating different Se-motifs into bioactive molecules as well as known drugs, thus expanding further knowledge about the design and molecular biology of Se-containing compounds. The results obtained during the experimental work are divided into three thematic blocks (Parts I, II, and III) and comprise sixty-three novel derivatives starting from the design, synthesis, purification, and characterization, to their preliminary assessment as therapeutic agents. Part I is dedicated to the foundational exploration of the Se chemistry, with a particular focus on its chemical versatility, therapeutic properties, and formulation strategies. This part encompasses three chapters (Chapters 1, 2, and 3) and lays the scientific groundwork supporting the experimental studies carried out in this Ph. D. project. Part II compromises two book chapters that are aimed at broadening the perspective of the research presented herein by situating it within the larger context of drug development. Two case studies (ebselen in Chapter 4 and fexinidazole in Chapter 5) are used to highlight the challenges and complexities ascribed to the journey from bench to bedside. An overview of the history of these experimental drugs, their pharmacological activities, and the main clinical outcomes from different clinical trials are covered in both chapters. Based on Chapter 3, two different strategies were followed to design the different series of compounds collected in Part III. On the one hand, we synthesized a total of 42 new derivatives based on flutamide, a well-known nonsteroidal antiandrogen drug, and the results are compiled in Part III.A (Chapters 6-8). All the compounds have been assessed as anticancer molecules, but certain compounds have also been evaluated as feasible antileishmanial candidates and carbonic anhydrase (CA) inhibitors. The second strategy, included in Part III.B (Chapters 9 and 10), was the direct manipulation of the structure of commercially available antibiotics, which rendered 21 novel selenoderivatives divided into two different series. Both chapters are dedicated to exploring the antibacterial properties of these novel compounds that present different Se-motifs in their scaffolds. In summary, the results compiled in this Ph.D. work confirm our initial hypothesis that incorporating different Se motifs into the scaffold of several active compounds can render new derivatives containing Se with feasible therapeutic activity. This Ph.D. memory is expected to provide a basis for future drug development and stimulate further research of new Se-containing compounds with biomedical applications.
