Synthesis of Oxadiazole-Based-Thiourea, Evaluation of Their β-Glucuronidase Inhibitory Potential, and Molecular Docking Study

Oxadiazole-based-thiourea analogs (1–18) were synthesized and evaluated for their β-glucuronidase inhibitory activity. All analogs showed extensive β-glucuronidase inhibitory potential ranging between (IC₅₀ = 2.20 ± 0.01 µM) to (IC₅₀ = 52.25 ± 1.20 µM) by comparing with the standard D-Saccharic acid 1,4-lactone (IC₅₀ = 48.30 ± 1.25 µM). Among the series, analogue 7 having IC₅₀ value (IC₅₀ = 2.20 ± 0.01 µM)), 16 (IC₅₀ = 4.40 ± 0.10 µM) and 4 (IC₅₀ = 9.20 ± 0.20 µM) showed an excellent inhibitory potential greater than that of standard D-saccharic acid-1,4- lactone. Analogue 7 (IC₅₀ = 2.20 ± 0.01 µM) of this series having flouro group at ortho-position of phenyl ring was recognized to be most active analogue due to involvement of flouro group in hydrogen bonding with the enzyme active site. In addition, all synthesized derivatives characterized by using High Resolution Mass Spectrometry (HR-MS), ¹³C-NMR and Nuclear Magnetic Resonance Spectroscopy (¹H-NMR proton). For better understanding of binding mode of interactions of these active analogs molecular docking study was performed. Structure Activity relationship (SAR) was also discussed.