Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking

Benzothiazole derivatives 1-26 have been synthesized and their in vitro beta-glucuronidase potential has been evaluated. Compounds 4 (IC50 = 8.9 +/- 0.25 mu M), 5 (IC50 = 36.1 +/- 1.80 mu M), 8 (IC50 = 8.9 +/- 0.38 mu M), 13 (IC50 = 19.4 +/- 1.00 mu M), 16 (IC50 = 4.23 +/- 0.054 mu M), and 18 (IC50 = 2.26 +/- 0.06 mu M) showed b-glucuronidase activity potent than the standard (D-saccharic acid 1,4-lactone, IC50 = 48.4 +/- 1.25 mu M). Compound 9 (IC50 = 94.0 +/- 4.16 mu M) is found to be the least active among the series. All active analogs were also evaluated for cytotoxicity and none of the compounds showed any cytotoxic effect. Furthermore, molecular docking studies were performed using the GOLD 3.0 program to investigate the binding mode of benzothiazole derivatives. This study identifies a novel class of beta-glucuronidase inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.