Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 4 , Pages 283-294, December 2008

SOD Activity of carboxyfullerenes predicts their neuroprotective efficacy: a structure-activity study

  • Sameh Saad Ali, PhD

      Affiliations

    • Department of Medicine, University of California, San Diego, California
    • Corresponding Author InformationCorresponding author. Division of Geriatrics, Department of Medicine, University of California, SCRB/SOM, Mailcode 0746, La Jolla, California, USA 92093-0746.
    • ,
  • Joshua I. Hardt, BS

      Affiliations

    • Department of Neurology, Washington University School of Medicine, St. Louis Missouri
    • ,
  • Laura L. Dugan, MD

      Affiliations

    • Department of Medicine, University of California, San Diego, California
    • Departments of Medicine and Neurosciences, University of California, San Diego, California, USA

Received 13 March 2008; accepted 9 May 2008. published online 25 July 2008.

Abstract 

Superoxide radical anion is a biologically important oxidant that has been linked to tissue injury and inflammation in several diseases. Here we carried out a structure-activity study on six different carboxyfullerene superoxide dismutase (SOD) mimetics with distinct electronic and biophysical characteristics. Neurotoxicity via N-methyl-d-aspartate receptors, which involves intracellular superoxide, was used as a model to evaluate structure-activity relationships between reactivity toward superoxide and neuronal rescue by these drugs. A significant correlation between neuroprotection by carboxyfullerenes and their ki toward superoxide radical was observed. Computer-assisted molecular modeling demonstrated that the reactivity toward superoxide is sensitive to changes in dipole moment, which are dictated not only by the number of carboxyl groups but also by their distribution on the fullerene ball. These results indicate that the SOD activity of these cell-permeable compounds predicts neuroprotection, and establishes a structure-activity relationship to aid in future studies on the biology of superoxide across disciplines.

Key words: Superoxide, Neuroprotection, Carboxyfullerenes, SOD mimetics

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 This work was funded by a Paul Beeson Physician Scholar Award, the Selma I. Hartke fund for aging research, and NIH NS47966 (L.L.D.).

PII: S1549-9634(08)00083-X

doi:10.1016/j.nano.2008.05.003

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 4 , Pages 283-294, December 2008

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