Agents and Actions

, Volume 26, Issue 3–4, pp 378–385 | Cite as

The interaction of the cardioprotective agent ICRF-187 ((+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane); its hydrolysis product (ICRF-198); and other chelating agents with the Fe(III) and Cu(II) complexes of adriamycin

  • Brian B. Hasinoff
Inflammation and Immunomodulation


Membrane-permeable ICRF-187 ((+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane) has shown promise as a cardioprotective agent against adriamycin-induced cardiotoxicity. ICRF-187 may act through its rings-opened hydrolysis product (ICRF-198) which has an EDTA-type structure and, likewise, strongly binds metal ions. The reactions of these compounds with Fe3+-adriamycin, and Cu2+-adriamycin complexes were examined. ICRF-198 quickly and completely removed both Fe3+ and Cu2+ from their complexes with adriamycin. ICRF-187 also reacted directly., but more slowly, with Fe3+-adriamycin to remove Fe3+ from the complex. This reaction was first order in ICRF-187 and Fe3+-adriamycin and yielded a second order rate constant of 123M−1 min−1. Metal ion-complex promoted hydrolysis may thus contribute to thein vivo hydrolysis of ICRF-187 to its metal ion-chelating active rings-opened form. Both ICRF-187 and ICRF-198 were very effective in preventing the Fe3+-adriamycin induced inactivation of the cytochromec oxidase activity of submitochondrial particles. A number of other chelating agents (desferal; pencillamine; DTPA; EDTA; TPEN; bathophenanthroline sulfonic acid; 2,2'-bipyridine; 1,10-phenanthroline, glutathione and 2-mercaptoethanol) were also examined for their ability to remove Fe3+ and Cu2+ from their complexes with adriamycin.


Sulfonic Acid Adriamycin DTPA Hydrolysis Product Cytochromec Oxidase 
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Copyright information

© Berkhäuser Verlag 1989

Authors and Affiliations

  • Brian B. Hasinoff
    • 1
  1. 1.Department of Chemistry and Faculty of MedicineMemorial University of NewfoundlandSt. John'sCanada

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