Synthesis and radiolabelled evaluation of novel pyrimidine derivatives as dual α-amylase inhibitors and GIT-targeted molecular imaging probe

Abstract

This study successfully developed synthetic pathways for novel pyrimidine-based compounds for their potential anti-diabetic α-amylase inhibitory activity, aiming at potential antidiabetic applications. Molecular docking techniques showed that compounds 1, 6, and 8 showed the highest molecular docking in silico binding affinity, followed by in vitro estimation. Compound 1 showed the strongest inhibitory in vitro amylase effect, in comparison to the reference drug acarbose. According to in silico and in vitro combination, a novel radiolabeled compound, ¹³¹Iodine-Compound 1, was chosen for further labeling study. The radiolabeling factors, including ligand concentration, pH, and reaction time, were adjusted to achieve maximum radiochemical yield and stability. For the in vivo behavior, biodistribution studies were estimated in mice up to a 36 hours period. The labelled compound showed significant and prolonged accumulation in the gastrointestinal tract, particularly the stomach and intestine, consistent with its proposed mechanism of enzyme inhibition. A gradual increase in muscle uptake was observed, raising possible insights into side effects reported with similar drugs. These results suggest that compound 1 not only possesses potent amylase-blocking and related effective antidiabetic activity but also holds promise as a molecular probe for molecular dynamic imaging for the GIT system.