One-pot synthesis of thioxo-tetrahydropyrimidine derivatives as potent β-glucuronidase inhibitor, biological evaluation, molecular docking and molecular dynamics studies.

A series of N,N-diethyl phenyl thioxo-tetrahydropyrimidine carboxamide have been synthesized and investigated for their β-glucuronidase inhibitory activities. All molecules exhibited excellent inhibition with IC values ranging from 0.35 to 42.05 µM and found to be even more potent than the standard d-saccharic acid. Structure-activity relationship analysis indicated that the meta-aryl-substituted derivatives significantly influenced β-glucuronidase inhibitory activities while the para-substitution counterpart outperforming moderate potency. The most potent compound in this series was 4g bearing thiophene motif with IC of 0.35 ± 0.09 µM. To verify the SAR, molecular docking and molecular dynamics studies were also performed.