Synthesis of pyrimidine-2,4,6-trione derivatives: Anti-oxidant, anti-cancer, α-glucosidase, β-glucuronidase inhibition and their molecular docking studies

• A series of pyrimidine-2,4,6-trione scaffold were synthesized.
• X-ray crystal structure of 3j, 3n and 3o were reported.
• Compound 3m (IC50 = 22.9 ± 0.5 μM) was identified as α-glucusidase inhibitor.
• Compound 3f (IC50 = 86.9 ± 4.33 μM) was identified as β-glucuronidase inhibitor.
• Molecular docking was carried out to investigate bonding mode of barbiturate acid.

This paper describes a facile protocol, efficient, and environmentally benign for the synthesis a series of barbiturate acid substituted at C5 position 3a–o. The desired compounds subjected in vitro for different set of bioassays including against anti-oxidant (DPPH and super oxide scavenger assays), anti-cancer, α-glucosidase and β-glucuronidase inhibitions. Compound 3m (IC50 = 22.9 ± 0.5 μM) found to be potent α-glucosidase enzyme inhibitors and showed more activity than standard acarbose (IC50 = 841 ± 1.73 μM). Compound 3f (IC50 = 86.9 ± 4.33 μM) found to be moderate β-Glucuronidase enzyme inhibitors and showed activity comparatively less than the standard d-saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 μM). Furthermore, in sillico investigation was carried out to investigate bonding mode of barbiturate acid derivatives.

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