alexa Protection by flavonoids against anthracycline cardiotoxicity: from chemistry to clinical trials.
Oncology

Oncology

Journal of Cancer Science & Therapy

Author(s): Bast A, Haenen GR, Bruynzeel AM, Van der Vijgh WJ, Bast A, Haenen GR, Bruynzeel AM, Van der Vijgh WJ

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Abstract Cardiotoxic side-effects of doxorubicin limit the clinical use of this anti-cancer agent. Iron chelators have been studied as protectors against doxorubicin-induced cardiotoxicity. These iron chelators do not provide optimal protection and have certain drawbacks. We therefore looked for new protectors and decided that these new compounds should combine iron chelating and antioxidant activity. Flavonoids appeared to possess those combined iron chelating and antioxidant properties. Quantum chemical evaluation of radical stabilization and determination of physico-chemical properties of a series of flavonoids brought our attention to the semi-synthetic flavonoid 7-monohydroxyetylrutoside (monoHER). Both in vitro (using an electrically paced mouse left atrium model) and in vivo (using a mouse ECG telemetry model) experiments corroborated the protective effect of monoHER. MonoHER also showed anti-inflammatory properties. A subsequent clinical phase I study showed that an i.v. dose of 1,500mg/m2 is a feasible and safe dose to be evaluated in a phase II study to investigate the protective properties of monoHER against doxorubicin-induced cardiotoxicity in cancer patients. This article was published in Cardiovasc Toxicol and referenced in Journal of Cancer Science & Therapy

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