María Elena Márquez Fernández

Synthesis and cytotoxic activity of tri-acyl ester derivatives of uridine in breast cancer cells

espanolObjetivos: Sintetizar derivados triesterificados de la uridina y evaluar su citotoxicidad sobre una linea celular de cancer de mama. Metodos: Se prepararon derivados triesterificados de la uridina mediante la esterificacion de Steglich para los acidos grasos y aromaticos, y con anhidrido acetico. Ademas se preparo el derivado acetonido mediante catalisis acida. Los compuestos se caracterizaron por espectroscopia de RMN (RMN ¹H y RMN 13C), y espectrometria de masas. Los derivados se evaluaron sobre lineas celulares de tumor de ovario de hamster chino (CHO) y de cancer de mama (MCF-7). Resultados: Se obtuvieron cinco derivados triesterificados de la uridina, uno con acido acetico, tres con acidos grasos (acido miristico, acido estearico y acido oleico) y uno con acido aromatico. Los derivados de uridina per-acetilada y acetonido se obtuvieron con rendimientos altos, sin embargo los derivados con acidos grasos y aromatico, se obtuvieron con rendimientos moderados y bajo, respectivamente. El acetonido y los compuestos 2 y 3, exhibieron inhibicion significativa de la viabilidad celular sobre ambas lineas a la concentracion mas alta evaluada. Conclusiones: El metodo de esterificacion con agentes de acoplamiento utilizado, permitio obtener derivados triesterificados de la uridina con acidos grasos y aromaticos. No se observo actividad citotoxica significativa (p EnglishAims: Synthesize tri-acyl ester derivatives of uridine, and evaluate its cytotoxicity against breast cancer cells line. Methods: The tri-esterified uridine derivatives were obtained through Steglich esterification reaction by fatty and aromatic acids, and with acetic anhydride. An acetonide derivative from uridine was prepared with acid catalysis. Compounds were characterized by NMR spectroscopy (¹H NMR and 13C NMR), and mass spectrometry. Derivatives were assessed in chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results: Five tri-acyl ester derivatives of uridine were obtained one acetic acid, three fatty acids (myristic acid, stearic acid and oleic acid) with an aromatic acid. The uridine per-acetylated and uridine acetonide were obtained in high yields, however, the tri-acyl ester derivatives of uridine with fatty and aromatic acids were obtained in moderate and low yields, respectively. The acetonide and compounds 2 and 3 exhibited a cell viability inhibition significant on both cell lines to the higher concentration. Conclusions: Esterification method with coupling agents allowed obtained tri-acyl ester uridine derivatives with aliphatic and aromatic acids. However, significant cytotoxic activity (p