Synthesis, β-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs

• Published in: Bioorganic Chemistry
• Main Author: Taha M.; Ismail N.H.; Imran S.; Rahim F.; Wadood A.; Khan H.; Ullah H.; Salar U.; Khan K.M.
• Format: Article
• Language: English
• Published: Academic Press Inc. 2016
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84978872852&doi=10.1016%2fj.bioorg.2016.07.008&partnerID=40&md5=f8a4038427a07f754f92a8c5f386c6af
• ISSN: 452068
• DOI: 10.1016/j.bioorg.2016.07.008

Hybrid bisindole-thiosemicarbazides analogs (1–18) were synthesized and screened for β-glucuronidase activity. All compounds showed varied degree of β-glucuronidase inhibitory potential when compared with standard D-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Compounds 4, 7, 9, 6, 5, 12, 17 and 18 showed exceptional β-glucuronidase inhibition with IC50 values ranging from 0.1 to 5.7 μM. Compounds 1, 3, 8, 16, 13, 2 and 14 also showed better activities than standard with IC50 values ranging from 7.12 to 15.0 μM. The remaining compounds 10, 11, and 15 showed good inhibitory potential with IC50 values 33.2 ± 0.75, 21.4 ± 0.30 and 28.12 ± 0.25 μM respectively. Molecular docking studies were carried out to confirm the binding interaction of the compounds. © 2016 Elsevier Inc.