Synthesis of bis-indolylmethanes as new potential inhibitors of β-glucuronidase and their molecular docking studies

• Published in: European Journal of Medicinal Chemistry
• Main Author: Taha M.; Ullah H.; Al Muqarrabun L.M.R.; Khan M.N.; Rahim F.; Ahmat N.; Ali M.; Perveen S.
• Format: Article
• Language: English
• Published: Elsevier Masson s.r.l. 2018
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85033591574&doi=10.1016%2fj.ejmech.2017.10.071&partnerID=40&md5=25123fa8f7fff0f74d5ed0f20b7ab3da
• ISSN: 2235234
• DOI: 10.1016/j.ejmech.2017.10.071

Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1–32 were synthesized and characterized by 1HNMR, 13CNNMR and HREI-MS. All compounds were evaluated in vitro for β-glucuronidase inhibitory potential. All analogs showed varying degree of β-glucuronidase inhibitory potential ranging from 0.10 ± 0.01 to 48.50 ± 1.10 μM when compared with the standard drug D-saccharic acid-1,4-lactone (IC50 value 48.30 ± 1.20 μM). Derivatives 1–32 showed the highest β-glucuronidase inhibitory potentials which is many folds better than the standard drug D-saccharic acid-1,4-lactone. Further molecular docking study validated the experimental results. It was proposed that bis-indolylmethane may interact with some amino acid residues located within the active site of β-glucuronidase enzyme. This study has culminated in the identification of a new class of potent β-glucuronidase inhibitors. © 2017 Elsevier Masson SAS