Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and

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Jan Olof G Karlsson1, Louis J Ignarro2, Ingemar Lundström3

  • 1Division of Drug Research/Pharmacology, Linköping University, Linköping, Sweden.

Drug Discovery Today
|December 3, 2014
PubMed

Insights

Manganese compounds like mangafodipir (MnDPDP) and calmangafodipir [Ca4Mn(DPDP)5] show superoxide dismutase (SOD) mimetic activity, helping manage reactive oxygen species. These agents are being explored for cancer therapy and treating heart conditions.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to pathological tissue damage.
  • Mitochondrial manganese superoxide dismutase (MnSOD) is crucial for controlling ROS and RNS levels.
  • Mangafodipir (MnDPDP) and its metabolite manganese pyridoxyl ethyldiamine (MnPLED) exhibit SOD mimetic activity.

Purpose of the Study:

  • To investigate the therapeutic potential of MnDPDP and its derivatives as SOD mimetics.
  • To evaluate the efficacy of calmangafodipir [Ca4Mn(DPDP)5] as a chemotherapy adjunct.
  • To explore the role of manganese complexes in managing oxidative stress in disease.

Main Methods:

  • Development of MnDPDP as a magnetic resonance imaging (MRI) contrast agent.
  • Assessment of SOD mimetic activity of MnDPDP and MnPLED.
  • Clinical trials evaluating MnDPDP as an adjunct in cancer and myocardial infarction.
  • Stabilization of manganese with DPDP in Ca4Mn(DPDP)5 for enhanced therapeutic activity.

Main Results:

  • MnDPDP and MnPLED demonstrated significant SOD mimetic activity.
  • MnDPDP showed promising results as an adjunct in cancer chemotherapy and myocardial infarction treatment.
  • Ca4Mn(DPDP)5 exhibits superior therapeutic activity due to stabilization of Mn(2+).

Conclusions:

  • Manganese complexes like MnDPDP and Ca4Mn(DPDP)5 possess therapeutic potential beyond their use as MRI contrast agents.
  • Ca4Mn(DPDP)5 is a promising candidate for cancer therapy, currently under investigation in Phase II clinical trials for metastatic colorectal cancer.

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