In Vitro Antioxidant and Pancreatic Anticancer Activity of Novel 5-Fluorouracil-Coumarin Conjugates.

Autor: López S; Departamento de Ingeniería Química, Instituto de Tecnología Química y Medioambiental (ITQUIMA), Universidad de Castilla-La Mancha, Avda. Camilo José Cela 1A, 13071 Ciudad Real, Spain., Gracia I; Departamento de Ingeniería Química, Instituto de Tecnología Química y Medioambiental (ITQUIMA), Universidad de Castilla-La Mancha, Avda. Camilo José Cela 1A, 13071 Ciudad Real, Spain., Plaza-Pedroche R; Área de Química Orgánica, Facultad de Ciencias y Tecnologías Químicas, Universidad de Castilla-La Mancha, Avda. Camilo José Cela 10, 13071 Ciudad Real, Spain., Rodríguez JF; Departamento de Ingeniería Química, Instituto de Tecnología Química y Medioambiental (ITQUIMA), Universidad de Castilla-La Mancha, Avda. Camilo José Cela 1A, 13071 Ciudad Real, Spain., Pérez-Ortiz JM; Unidad de Investigación Traslacional, Hospital General Universitario de Ciudad Real, C/Obispo Rafael Torija s/n, 13005 Ciudad Real, Spain., Rodríguez-López J; Área de Química Orgánica, Facultad de Ciencias y Tecnologías Químicas, Universidad de Castilla-La Mancha, Avda. Camilo José Cela 10, 13071 Ciudad Real, Spain., Ramos MJ; Departamento de Ingeniería Química, Instituto de Tecnología Química y Medioambiental (ITQUIMA), Universidad de Castilla-La Mancha, Avda. Camilo José Cela 1A, 13071 Ciudad Real, Spain.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2022 Oct 10; Vol. 14 (10). Date of Electronic Publication: 2022 Oct 10.
DOI: 10.3390/pharmaceutics14102152
Abstrakt: Molecular hybridization consists of the combination of two or more non-identical pharmacophores in a single molecule. It has emerged as a promising strategy that allows the design of molecular frameworks with enhanced activity and affinity compared to their parent drugs. In this work, two novel hybrids that combine the well-known anticancer chemotherapeutic agent 5-fluorouracil with antioxidant coumarin derivatives have been synthesized and characterized by means of a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The conjugates showed good antioxidant properties and a high tendency to aggregate and form stable nanoparticles in aqueous media, with regular shape and uniform size. These materials have proven to be preferential cytotoxic agents in vitro against human pancreatic cancer cells PANC-1, with an activity superior to free 5-fluorouracil. These results open up the possibility of exploiting the synergistic combination between 5-fluorouracil and coumarin derivatives and warrant further investigation of these hybrids as promising pancreatic anticancer agents.
Databáze: MEDLINE
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