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

Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1-32 were synthesized and characterized by (HNMR)-H-1, (CNNMR)-C-13 and HREI-MS. All compounds were evaluated in vitro for beta-glucuronidase inhibitory potential. All analogs showed varying degree of beta-glucuronidase inhibitory potential ranging from 0.10 +/- 0.01 to 48.50 +/- 1.10 mu M when compared with the standard drug D-saccharic acid-1,4-lactone (IC50 value 48.30 +/- 1.20 mu M). Derivatives 1-32 showed the highest P-glucuronidase inhibitory potentials which is many folds better than the standard drug n-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 beta-glucuronidase enzyme. This study has culminated in the identification of a new class of potent beta-glucuronidase inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.