Nuevos sistemas bioorganometálicos derivados del fragmento 1,2,4-Triazol: diseño, síntesis, caracterización, estudio de propiedades anticancerígenas y como potencial inhibidor de la aromatasa.
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Date
2025
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Universidad de Concepción
Abstract
En el presente trabajo de investigación, se planteó la síntesis y caracterización de precursores carbinoles organometálicos y su posterior derivación hacia azoles organometálicos que contienen los grupos ciretrenilo y cimantrenilo, junto con el fragmento bioactivo 1,2,4-triazol. Además, se llevó a cabo la evaluación de dichos azoles tanto en términos de sus propiedades anticancerígenas y como inhibidores de la aromatasa.
Con este enfoque, se desarrolló una estrategia bioorganometálica orientada a la búsqueda de nuevos sistemas con potencial aplicación en la investigación oncológica, permitiendo no solo su síntesis y caracterización, sino también la evaluación de sus propiedades biológicas.
Las rutas sintéticas diseñadas, plantearon en una primera etapa la obtención de los carbinoles de tipo [(CO)3M(5-C5H4)-CH(OH)-R] donde M = Re (I) y Mn(I); R = (C6H4-4-CN), (5-C5H4)Re(CO)3. Estos derivados fueron sintetizados mediante la reacción entre los precursores [(CO)3M(5-C5H4 CHO)] (M = Mn (I) y Re(I)) y [(CO)3Re(5-C5H4-Br)] o 4-bromobenzonitrilo, según sea el caso, por medio de una reacción de adición nucleofílica. Finalmente, se llevó a cabo sobre dichos carbinoles, una aminación directa utilizando 1,2,4-triazol, en presencia de triflato de aluminio (III).
A todos los azoles obtenidos se les realizó un estudio de estabilidad en medio acuoso a través de UV-Vis, para finalmente ser evaluados por sus propiedades anticancerígenas (células cancerígenas ER+ MCF-7) y como inhibidores de la aromatasa. Los ensayos se llevaron a cabo en colaboración con el Dr. Felipe Zúñiga de la Facultad de Farmacia de la Universidad de Concepción.
In this research work, the synthesis and characterization of organometallic carbinol precursors were proposed, followed by their derivation into organometallic azoles incorporating the cyrhetrenyl and cymantrenyl groups, along with the bioactive 1,2,4-triazole fragment. Additionally, these azoles were evaluated both in terms of their anticancer properties and as aromatase inhibitors. With this approach, a bioorganometallic strategy was developed to search for new systems with potential applications in oncology research, enabling not only their synthesis and characterization but also the evaluation of their biological properties. The designed synthetic routes initially involved obtaining carbinols of the type [(CO)3M(5-C5H4)-CH(OH)-R], where M = Re (I) and Mn (I); R = (C6H4-4 CN), (5-C5H4)Re(CO)3. These derivatives were synthesized via the reaction between the precursors [(CO)3M(5-C5H4-CHO)] (M = Mn (I) and Re (I)) and either [(CO)3Re(5-C5H4-Br)] or 4-bromobenzonitrile, as appropriate, through a nucleophilic addition. Finally, these carbinols underwent direct amination using 1,2,4-triazole in the presence of aluminum triflate. All the obtained azoles were subjected to a stability study in an aqueous medium via UV-Vis analysis, before being evaluated for their anticancer properties (ER+ MCF-7 cancer cells) and as aromatase inhibitors. The assays were conducted in collaboration with Dr. Felipe Zúñiga from the Faculty of Pharmacy at the University of Concepción.
In this research work, the synthesis and characterization of organometallic carbinol precursors were proposed, followed by their derivation into organometallic azoles incorporating the cyrhetrenyl and cymantrenyl groups, along with the bioactive 1,2,4-triazole fragment. Additionally, these azoles were evaluated both in terms of their anticancer properties and as aromatase inhibitors. With this approach, a bioorganometallic strategy was developed to search for new systems with potential applications in oncology research, enabling not only their synthesis and characterization but also the evaluation of their biological properties. The designed synthetic routes initially involved obtaining carbinols of the type [(CO)3M(5-C5H4)-CH(OH)-R], where M = Re (I) and Mn (I); R = (C6H4-4 CN), (5-C5H4)Re(CO)3. These derivatives were synthesized via the reaction between the precursors [(CO)3M(5-C5H4-CHO)] (M = Mn (I) and Re (I)) and either [(CO)3Re(5-C5H4-Br)] or 4-bromobenzonitrile, as appropriate, through a nucleophilic addition. Finally, these carbinols underwent direct amination using 1,2,4-triazole in the presence of aluminum triflate. All the obtained azoles were subjected to a stability study in an aqueous medium via UV-Vis analysis, before being evaluated for their anticancer properties (ER+ MCF-7 cancer cells) and as aromatase inhibitors. The assays were conducted in collaboration with Dr. Felipe Zúñiga from the Faculty of Pharmacy at the University of Concepción.
Description
Tesis presentada para optar al grado de Magister en Ciencias con mención en Química
Keywords
Química organometálica, Triazol, Aromatasa