Synthesis, in vitro β-glucuronidase inhibition of benzoxazole bearing thiosemicarbazide derivatives along with in silico molecular docking study

This study was aimed to design and synthesize hybrid analogues of benzoxazole bearing thiosemicarbazide analogues 1–15 as promising β-Glucuronidase inhibitory activity using D-saccharic acid 1,4-lactone as the reference inhibitor. The newly afforded benzoxazole-thiosemicarbazide compounds 1–15 displayed a broad range of inhibitory potential with IC50 values ranging from 20.58 ± 2.46 to 87.89 ± 8.43 μM, as compared to D-saccharic acid 1,4-lactone (IC50 = 59.5 ± 5.36 μM). Among the synthesized series, the compounds 14, 2, and 5 demonstrated outstanding β-Glucuronidase inhibitory potential with IC50 values of 20.58 ± 2.46, 25.24 ± 2.34 and 24.53 ± 2.53 μM respectively. Further, the precise structures of synthesized analogues were confirmed using 1H NMR, 13C NMR and HREIMS. Additionally, the molecular docking approach was employed to correlate the in vitro β-Glucuronidase inhibitory activity well with in silico study and result obtained corroborated that active analogues established several key interactions with the active sites of β-Glucuronidase enzyme.