Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells

ABSTRACT: Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. First, it was accomplished the halogenation reaction on the 5-position of the nitrogenous base, subsequently, the ester and amide derivatives were performed for all hydroxyl and amine group present in the nucleosides. Besides, the uridine acetonide derivatives as prepared by acid catalysis. The prod ucts were characterized by nuclear magnetic resonance spectroscopy (1H RMN y 13C RMN) and mass spectrometry in positive mode by direct injection. Derivatives were evaluated in Chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results. The four derivatives were obtained with chlorine and bromine for the uridine and cytarabine, respectively, their respective per-acetylated derivatives, the per-acetylated nucleoside and the uridine acetonide; the compounds were obtained with efficiency over 90%. The per-acetylated nucleosides and the halogenated and per-acetylated derivatives did not show inhibitory effects on cell viability in MCF-7 cell line. However, the per-acetylated and halo genated derivatives presented a higher cytotoxic activity than their respective per-acetylated nucleoside. The uridine 3’,4’-acetonide showed a significant cytotoxicity on both cell lines.Conclusions. The per-acetylated nucleoside, and the respective halogenated derivatives with chlorine and bromine were obtained with high yields, nevertheless, these compounds did not exhibit a significant anti-proliferative activity (p˂0.05), possibly due to a low intra-cellular activation.

• Autores: Berrío Escobar, Jhon Fernando; Pastrana Restrepo, Manuel Humberto; Galeano Jaramillo, Elkin de Jesús; Márquez Fernández, Diana Margarita; Márquez Fernández, María Elena; Martínez Martínez, Alejandro
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2017
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/24051
• Acceso en línea: http://hdl.handle.net/10495/24051; http://revistaseug.ugr.es/index.php/ars/article/view/6441
• Palabra clave: Neoplasias de la Mama; Breast Neoplasms; Nucleósidos; Nucleosides; Uridina; Uridine; Citarabina; Cytarabine; Citotoxicidad; Cytotoxicity; http://aims.fao.org/aos/agrovoc/c_34251
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-sa/2.5/co/