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

• Published in: Bioorganic and Medicinal Chemistry Letters
• Main Author: Khan K.M.; Rahim F.; Wadood A.; Taha M.; Khan M.; Naureen S.; Ambreen N.; Hussain S.; Perveen S.; Choudhary M.I.
• Format: Article
• Language: English
• Published: Elsevier Ltd 2014
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897370463&doi=10.1016%2fj.bmcl.2014.02.015&partnerID=40&md5=2dabf22e5b34452708bb8e78f6af9300
• ISSN: 0960894X
• DOI: 10.1016/j.bmcl.2014.02.015

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. © 2014 Elsevier Ltd. All rights reserved.