Chalcone-Coumarin Derivatives as Potential Anti-Cancer Drugs: An in vitro and in vivo Investigation
Vincent Jamier, Wioleta Marut, Sergio Valente, Christiane Chereau, Sandrine Chouzenoux, Carole Nicco, Herve Lemarechal, Bernard Weill, Gilbert Kirsch, Claus Jacob and Frederic Batteux
Affiliation: Laboratoire d’Immunologie, 24 rue du faubourg St Jacques 75679 Paris cedex 14, France.
Cancer cells display an overproduction of reactive oxygen species resulting from an exaggerated intrinsic oxidative stress.
However, the concept of deleterious oxidants versus beneficial antioxidants has recently evolved. Indeed, molecules like natural
coumarins have shown anti-oxidant or pro-oxidant properties depending on their intracellular concentration. Therefore, we have
investigated the structure-activity relationship of a variety of coumarin derivatives in terms of cytotoxicity towards human and murine
carcinoma cell lines (HT29, HepG2, A549, MCF7, OVCAR and CT26). Amongst those compounds, (E)-7-methoxy-4-(3-oxo-3-
phenylprop-1-enyl)-2H-chromen-2-one and (E)-7-hydroxy-4-(3-(4-hydroxyphenyl)-3-oxoprop-1-enyl)-2H-chromen-2-one displayed the
most potent cytotoxic effect on colon cancer cells, CT26, (IC50=4.9µM) linked to their pro-oxidant properties. Those compounds
triggered the in vitro production of reactive oxygen species by tumor cells, leading to their death through a necrotic process. In vivo,
molecules also slowed down tumor growth by 65.7% and 35.4%, respectively, without inducing significant side effects.
Keywords: Cancer, coumarin, cytotoxicity, oxidative stress, structure-activity relationship.
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