Synthesis and protective effects of coumarin derivatives against oxidative stress induced by doxorubicin.
The use of doxorubicin (DOX) in the treatment of solid tumors is limited by cardiotoxicity essentially due to oxidative stress generation. The aim of this study was to identify coumarin derivatives displaying a protective antioxidant activity without affecting DOX antitumoral efficiency. A set of eighteen coumarinic derivatives was synthesized. Their antioxidant power was evaluated in vitro with the FRAP (ferric reducing ability of plasma) method and in human breast adenocarcinoma MCF7 cells using H(2)DCFDA (2',7'-dichlorodihydrofluorescein diacetate) in a cytometric analysis. 4-Methyl-7,8-dihydroxycoumarin was found to exhibit an important antioxidant strength, a low cytotoxicity, and could decrease ROS (reactive oxygen species) production generated by DOX treatment without affecting DOX cytotoxicity in MCF7 cells.
Beillerot
Adeline
A
Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, Université Paul Verlaine - Metz, Institut Jean Barriol FR CNRS 2843, UFR SciFA, Campus Bridoux, rue du Général Delestraint, 57070 Metz, France.
Domínguez
Juan-Carlos Rodríguez
JC
Kirsch
Gilbert
G
Bagrel
Denyse
D
D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
C527385:4-methyl-7,8-dihydroxycoumarin; D000975:Antioxidants; D003374:Coumarins; D017382:Reactive Oxygen Species; D004317:Doxorubicin