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Carbon-14 radiolabeling and tissue distribution evaluation of MMV390048.

Authors
  • Sonopo, Molahlehi S1
  • Pillay, Adushan1
  • Chibale, Kelly2
  • Marjanovic-Painter, Biljana1
  • Donini, Cristina3
  • Zeevaart, Jan R4
  • 1 Radiochemistry, Necsa, Pretoria, South Africa. , (South Africa)
  • 2 Drug Discovery and Development Centre (H3D) and South African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry, University of Cape Town, Rondebosch, South Africa. , (South Africa)
  • 3 Translational Medicine, MMV, Geneva, Switzerland. , (Switzerland)
  • 4 DST/NWU, Preclinical Drug Development Platform, North-West University, Potchefstroom, South Africa. , (South Africa)
Type
Published Article
Journal
Journal of Labelled Compounds
Publisher
Wiley (John Wiley & Sons)
Publication Date
Dec 01, 2016
Volume
59
Issue
14
Pages
680–688
Identifiers
DOI: 10.1002/jlcr.3445
PMID: 27646069
Source
Medline
Keywords
License
Unknown

Abstract

The antimalarial compound MMV390048 ([14 C]-11) was labeled with carbon-14 isotope via a 3-step synthesis. It was obtained in a 15.5% radiochemical overall yield from carbon-14 labeled methyl iodide with a radiochemical purity of >99%. After single oral administration of [14 C]-11 to albino and pigmented rats its tissue distribution profile was studied. Tissue distribution results showed high local exposure in the GI tract and excretory organs but low exposure of all other tissues. The radioactivity uptake was higher in the eyes of the pigmented rats than in the eyes of the albino rats at all-time points. The highest accumulation reached in the eyes of the pigmented rats was 0.46% at 6 hours. However, these levels are still very low as compared to the other organs studied. There was very little radioactivity from MMV390048 ([14 C]-11) present in the skin of both the albino and pigmented rats. The results obtained are supportive of further development of MMV390048 as a potential antimalarial compound.

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