Indole bearing thiadiazole analogs: synthesis, β-glucuronidase inhibition and molecular docking study

Indole based thiadiazole derivatives (1-22) have synthesized, characterized by NMR and HREI-MS and evaluated for beta-Glucuronidase inhibition. All compounds showed outstanding beta-glucuronidase activity with IC50 values ranging between 0.5 +/- 0.08 to 38.9 +/- 0.8 A mu M when compared with standard d-saccharic acid 1,4 lactone (IC50 value of 48.1 +/- 1.2 A mu M). The compound 6, a 2,3-dihydroxy analog was found the most potent among the series with IC50 value 0.5 +/- 0.08 A mu M. Structure activity relationship has been established for all compounds. To confirm the binding interactions of these newly synthesized compounds, molecular docking study have been carried out which reveal that these compounds established stronger hydrogen bonding networks with active site residues.