Carbon-14 radiolabelling and tissue distribution evaluation of a potential anti-TB compound.
This paper describes a five-step synthesis of a carbon-14-labelled pyrazole compound (11). A total of 2.96 MBq of 11 was obtained with the specific activity of 2242.4 MBq/mmol. The radiochemical purity was >99%, and the overall radiochemical yield was 60% based on the [(14) C6 ] 4-bromoaniline starting material. Biodistribution results showed that the radiotracer (administrated orally) has a high accumulation in the small intestine, large intestine and liver of both non-infected and tuberculosis (TB)-infected mice. Therefore, this suggests that compound 11 undergoes hepatobiliary clearance. The compound under investigation has been found to be slowly released from the liver between 2 and 8 h. The study revealed that 11 has no affinity for TB cells.
Radiochemistry, Necsa, P. O. Box 482, Pretoria, 0001, South Africa.
Molahlehi S
MS
Sonopo
Medical Research Council of South Africa, Pretoria, South Africa.
Kobus
K
Venter
iThemba Pharmaceuticals (Pty) Ltd, Johannesburg, South Africa.
Susan
S
Winks
Radiochemistry, Necsa, P. O. Box 482, Pretoria, 0001, South Africa.
Biljana
B
Marjanovic-Painter
iThemba Pharmaceuticals (Pty) Ltd, Johannesburg, South Africa.
Garreth L
GL
Morgans
DST/NWU, Preclinical Drug Development Platform, North West University, Potchefstroom, South Africa.
Jan R
JR
Zeevaart
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling; D051379:Mice; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D011854:Radiochemistry; D014018:Tissue Distribution
D000995:Antitubercular Agents; D002250:Carbon Radioisotopes; D011720:Pyrazoles; C031280:pyrazole
C-14 labelling; pyrazole; tissue distribution; tuberculosis