2,5-Disubstituted thiadiazoles as potent ß-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 ß-glucuronidase enzyme. Most of the compounds including 1 (IC50 = 26.05 ±â€¯0.60 µM), 2 (IC50 = 42.53 ±â€¯0.80 µM), 4 (IC50 = 38.74 ±â€¯0.70 µM), 5 (IC50 = 9.30 ±â€¯0.29 µM), 6 (IC50 = 6.74 ±â€¯0.26 µM), 7 (IC50 = 18.40 ±â€¯0.66 µM), and 15 (IC50 = 18.10 ±â€¯0.53 µM) exhibited superior activity potential than the standard d-saccharic acid-1,4-lactone (IC50 = 48.4 ±â€¯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.