2,5-Disubstituted thiadiazoles as potent β-glucuronidase inhibitors; Synthesis, in vitro and in silico studies.

Twenty-five thiadiazole derivatives 1-25 were synthesized from methyl 4-methoxybenzoate via hydrazide and thio-hydrazide intermediates, and evaluated for their potential against β-glucuronidase enzyme. Most of the compounds including 1 (IC = 26.05 ± 0.60 μM), 2 (IC = 42.53 ± 0.80 μM), 4 (IC = 38.74 ± 0.70 μM), 5 (IC = 9.30 ± 0.29 μM), 6 (IC = 6.74 ± 0.26 μM), 7 (IC = 18.40 ± 0.66 μM), and 15 (IC = 18.10 ± 0.53 μM) exhibited superior activity potential than the standard d-saccharic acid-1,4-lactone (IC = 48.4 ± 1.25 μM). Molecular docking studies were conducted to correlate the in vitro results and to identify possible mode of interaction with enzyme active site.