Inhibitory Activity of Bioactive Phloroglucinols from the Rhizomes of Dryopteris crassirhizoma on Escherichia coli β-Glucuronidase: Kinetic Analysis and Molecular Docking Studies

초록

Phloroglucinols-one of the major secondary metabolites in Dryopteris crassirhizoma-exhibit various pharmacological effects, such as antiviral, antioxidant, and antidiabetic activities. This study evaluated 30 phloroglucinols isolated from the rhizomes of D. crassirhizoma for their inhibitory activity on beta-glucuronidase via in vitro assays. Among them, dimeric phloroglucinols 13-15 moderately inhibited beta-glucuronidase, and trimeric phloroglucinols 26-28 showed strong inhibitory effects, with IC50 values ranging from 5.6 to 8.0 mu M. Enzyme kinetic analysis confirmed all six active compounds to be in a competitive mode of inhibition. Molecular docking simulations revealed the key binding interactions with the active site of beta-glucuronidase protein and the binding mechanisms of these active metabolites. Our results suggest that the rhizomes of D. crassirhizoma and trimeric compounds 26-28 may serve as potential candidates for discovering and developing new beta-glucuronidase inhibitors.

키워드