Doxorubicin-antioxidant co-drugs

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Chegaev, Konstantin¹  Riganti, Chiara²  Rolando, Barbara¹  Lazzarato, Loretta¹  Gazzano, Elena²  Guglielmo, Stefano¹  Ghigo, Dario²  Fruttero, Roberta¹  Gasco, Alberto¹ 

[1] Univ Turin, Dept Sci & Drug Technol, I-10125 Turin, Italy

[2] Univ Turin, Dept Oncol, I-10126 Turin, Italy

关键词: Doxorubicin;    Ferulic acid;    Antioxidant;    Cardiotoxicity;    ABC transporters;   

DOI  :  10.1016/j.bmcl.2013.07.070

来源: Elsevier

【 摘 要 】

Doxorubicin-antioxidant multitarget compounds 6 and 7 were obtained by combining doxorubicin (DOX) with caffeic and ferulic acids through an ester linkage at C-14. The products were studied in in vitro models of cardiomyocytes and breast cancer cells, characterized by different degrees of resistance to DOX, due to different expressions of ATP binding cassette (ABC) transporters. Compound 7 was found to be less toxic than DOX in cardiomyocytes and to display the same possibly higher toxicity against the resistant breast cancer cells. This result shows that appropriate DOX-antioxidant co-drugs can limit the onset of cardiac damage, a significant side-effect of DOX, without impairing the antitumor activity of the parent antibiotic. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

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