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

Bioorg Med Chem Lett. 2014 Apr 1;24(7):1825-9. doi: 10.1016/j.bmcl.2014.02.015. Epub 2014 Feb 14.

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±0.04 μM), 6 (IC50=1.86±0.05 μM), 10 (IC50=2.80±0.29 μM), 9 (IC50=3.10±0.28 μM), 14 (IC50=4.30±0.08 μM), 2 (IC50=18.40±0.09 μM), 19 (IC50=19.90±1.05 μM), 4 (IC50=20.90±0.62 μM), 7 (IC50=21.50±0.77 μM), and 3 (IC50=22.30±0.02 μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50=48.40±1.25 μM). 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.

Keywords: Bisindole; Molecular docking; SAR; β-Glucuronidase inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Glucuronidase / antagonists & inhibitors*
  • Glucuronidase / metabolism
  • Glycoproteins / chemical synthesis
  • Glycoproteins / chemistry
  • Glycoproteins / pharmacology*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Glycoproteins
  • Indoles
  • beta-glucuronidase inhibitor
  • Glucuronidase