Evaluation of bisindole as potent β-glucuronidase inhibitors: Synthesis and in silico based studies

Abstract

Bisindole analogs 1–17 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50=1.62±0.04μM), 6 (IC50=1.86±0.05μM), 10 (IC50=2.80±0.29μM), 9 (IC50=3.10±0.28μM), 14 (IC50=4.30±0.08μM), 2 (IC50=18.40±0.09μM), 19 (IC50=19.90±1.05μM), 4 (IC50=20.90±0.62μM), 7 (IC50=21.50±0.77μM), and 3 (IC50=22.30±0.02μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50=48.40±1.25μM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent β-glucouronidase inhibitors.