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Molecules 2011, 16(4), 2982-2989; doi:10.3390/molecules16042982
Communication

Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease

1,* , 1, 1, 2 and 1
Received: 8 February 2011; in revised form: 31 March 2011 / Accepted: 2 April 2011 / Published: 6 April 2011
(This article belongs to the collection Bioactive Compounds)
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Abstract: The compounds 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl nitrate (C1), (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl nitrate (C2), 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (C3), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (C4), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (C5), and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]ethyl nitrate (C6) were evaluated with a micronucleus test using mouse peripheral blood to identify new candidate drugs for the treatment of sickle cell disease (SCD) that are safer than hydroxyurea. The compounds induced an average frequency of micronucleated reticulocytes (MNRET) of less than six per 1,000 cells at 12.5, 25, 50, and 100 mg/kg, whereas hydroxyurea induced an average MNRET frequency of 7.8, 9.8, 15, and 33.7 per 1000 cells respectively, at the same concentrations. Compounds C1–C6 are new non-genotoxic in vivo candidate drugs for the treatment of SCD symptoms.
Keywords: genotoxicity assay; micronucleus; sickle cell; phthalimide derivatives genotoxicity assay; micronucleus; sickle cell; phthalimide derivatives
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Dos Santos, J.L.; Longhin Bosquesi, P.; Varanda, E.A.; Moreira Lima, L.; Chung, M.C. Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease. Molecules 2011, 16, 2982-2989.

AMA Style

Dos Santos JL, Longhin Bosquesi P, Varanda EA, Moreira Lima L, Chung MC. Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease. Molecules. 2011; 16(4):2982-2989.

Chicago/Turabian Style

Dos Santos, Jean Leandro; Longhin Bosquesi, Priscila; Varanda, Eliana Aparecida; Moreira Lima, Lídia; Chung, Man Chin. 2011. "Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease." Molecules 16, no. 4: 2982-2989.


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