title: Carbon-14 radiolabeling and tissue distribution evaluation of MMV390048.
abstract: The antimalarial compound MMV390048 ([14C]-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 [14C]-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 ([14C]-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.
authors.affiliation: Radiochemistry, Necsa, Pretoria, South Africa.
authors.forename: Molahlehi S
authors.initials: MS
authors.lastname: Sonopo
authors.affiliation: Radiochemistry, Necsa, Pretoria, South Africa.
authors.forename: Adushan
authors.initials: A
authors.lastname: Pillay
authors.affiliation: 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.
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
authors.affiliation: Radiochemistry, Necsa, Pretoria, South Africa.
authors.forename: Biljana
authors.initials: B
authors.lastname: Marjanovic-Painter
authors.affiliation: Translational Medicine, MMV, Geneva, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Donini
authors.affiliation: DST/NWU, Preclinical Drug Development Platform, North-West University, Potchefstroom, South Africa.
authors.forename: Jan R
authors.initials: JR
authors.lastname: Zeevaart
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes / Q000737:chemistry*; D005260:Female; D007553:Isotope Labeling; D008297:Male; D051381:Rats; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000631:Aminopyridines; D000962:Antimalarials; D002250:Carbon Radioisotopes; C000625007:MMV390048; D013450:Sulfones
keywords: aminopyridine; antimalarial agent; carbon-14; plasmodium falciparum; tissue distribution