In vitro antioxidant and pancreatic anticancer activity of novel 5-fluorouracil-coumarin conjugates

Molecular hybridization consists of the combination of two or more non-identical pharmaco-phores in a single molecule. It has emerged as a promising strategy that allows the design of mo-lecular frameworks with enhanced activity and affinity compared to their parent drugs. In this work, two novel hy...

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Bibliographic Details
Authors: López Quijorna, Sonia, Plaza Pedroche, Rodrigo, Pérez Ortiz, José manuel, Gracia Fernández, Ignacio, Rodríguez López, Julián, Ramos Marcos, María Jesús, Rodríguez Romero, Juan Francisco
Format: article
Publication Date:2022
Country:España
Institution:Universidad de Castilla-La Mancha
Repository:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/32460
Online Access:https://doi.org/10.3390/pharmaceutics14102152
https://hdl.handle.net/10578/32460
Access Level:Open access
Keyword:5-Fluorouracil
Anticancer
Antioxidant
Click chemistry
Conjugates
Coumarins.
Description
Summary:Molecular hybridization consists of the combination of two or more non-identical pharmaco-phores in a single molecule. It has emerged as a promising strategy that allows the design of mo-lecular 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 aque-ous 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 combina-tion between 5-fluorouracil and coumarin derivatives and warrant further investigation of these hybrids as promising pancreatic anticancer agents.