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

摘要

A series of N,N-diethyl phenyl thioxo-tetrahydropyrimidine carboxamide have been synthesized and investigated for their beta-glucuronidase inhibitory activities. All molecules exhibited excellent inhibition with IC50 values ranging from 0.35 to 42.05 mu M 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 beta-glucuronidase inhibitory activities while the para-substitution counterpart outperforming moderate potency. The most potent compound in this series was 4g bearing thiophene motif with IC50 of 0.35 +/- 0.09 mu M. To verify the SAR, molecular docking and molecular dynamics studies were also performed.