Didox

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Background

Didox is a synthetic antioxidant.Polyhydroxylated aromatic compounds, both natural and synthetic, are important biological antioxidants.In vitro: In a previous study, the brain tissue from patients with HIV encephalitis was immunostained for lipid peroxidation. The presence of oxidized proteins in the CSF and CSF-induced progressive decrease in mitochondrial activity correlated with the severity of cognitive impairment. Didox together with L-deprenyl, imidate, diosgenin, and ebselen could block the CSF-induced toxicity. No effect of trimidox, ruthenium red, or Quercetin was seen [1]. Another study found that the exposure of didox prior or post to radiation in both PC-3/vector and PC-3/Bcl-2 transfectants led to an increase in radiation enhancement ratios. A significant reduction in G(2)M phase was observed in cells exposed to didox post IR when compared to cells exposed to IR alone. In addition, the exposure to didox after radiation in PC-3/vector significantly abrogated radiation-induced Bcl-2 upregulation [2].In vivo: In syngeneic, therapy-resistant AML models, single agent didox treatment led to a significant reduction in leukemia burden and a survival benefit. Didox was well tolerated and didox exposure at levels that impaired leukemia growth did not inhibit normal HSC engraftment [3].Clinical trial: So far, no clinical study has been conducted.

[1] Turchan, J. ,Pocernich, C.B.,Gairola, C., et al. Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants. Neurology 60, 307-314 (2003).
[2] Inayat, M. S.,Chendil, D.,Mohiuddin, M., et al. Didox (A novel ribonucleotide reductase inhibitor) Overcomes bcl-2 mediated radiation resistance in prostate cancer cell line PC-3. Cancer Biology and Therapy 1(5), 539-545 (2002).
[3] Cook GJ, Caudell DL, Elford HL, Pardee TS. The efficacy of the ribonucleotide reductase inhibitor Didox in preclinical models of AML. PLoS One. 2014 Nov 17;9(11):e112619.