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 β-Glucuronidase inhibition. All compounds showed outstanding β-glucuronidase activity with IC₅₀ values ranging between 0.5 ± 0.08 to 38.9 ± 0.8 µM when compared with standard d-saccharic acid 1,4 lactone (IC₅₀ value of 48.1 ± 1.2 µM). The compound 6, a 2,3-dihydroxy analog was found the most potent among the series with IC₅₀ value 0.5 ± 0.08 µM. 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.