Synthesis and structure investigation of novel pyrimidine-2,4,6-trione derivatives of highly potential biological activity as anti-diabetic agent

• Novel pyrimidine-2,4,6(1H,3H,5H)-trione derivative 3 was synthesized.
• X-Ray crystal structure of 3 was reported.
• The electronic and spectroscopic properties of 3 were predicted using DFT method.
• Compound 3 (IC50 = 305 ± 3.8 μM) was identified as a potent α-glucosidase inhibitor.
• Molecular docking of the synthesized compound 3 was discussed.

Synthesis of (±)-1,3-dimethyl-5-(1-(3-nitrophenyl)-3-oxo-3-phenylpropyl)pyrimidine-2,4,6(1H,3H,5H)-trione (3) is reported. The structure of compound 3 was deduced by using spectroscopic methods, X-ray crystallography, and DFT calculations. The calculated geometric parameters were found to be in good agreement with the experimental data obtained from the X-ray structure. The NBO calculations were performed to predict the natural atomic charges at the different atomic sites and to study the different intramolecular charge transfer (ICT) interactions. The high LP(3)O6 →z BD*(2)O5–N3 ICT interaction energy (165.36 kcal/mol) indicated very strong n → π* electron delocalization while the small LP(2)O → BD*(1)C–H ICT interaction energies indicated that the C–H … O intramolecular interactions are weak. The 1H and 13C NMR chemical shifts calculated using GIAO method showed good agreement with the experimental data. The calculated electronic spectra of the studied compound using TD-DFT method showed intense electronic transition band at 243.9 nm (f = 0.2319) and a shoulder at 260.2 nm (f = 0.1483) which were due to H-4/H-2/H-1/H → L+2 and H-5 → L electronic excitations, respectively. Compound 3 (IC50 = 305 ± 3.8 μM) was identified as a potent inhibitor of α-glucosidase in vitro and showed several fold more inhibition than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Molecular docking of the synthesized compound was discussed.

Compound 3 (IC50 = 305 ± 3.8 μM) was identified as a potent α-glucosidase inhibitor in vitro and showed several fold more inhibition than the standard drug acarbose (IC50 = 841 ± 1.73 μM).Figure optionsDownload as PowerPoint slide