A natural inhibitor from Alisma orientale against human carboxylesterase 2: Kinetics, circular dichroism spectroscopic analysis, and docking simulation

As a part of our searching for natural human carboxylesterase 2 (human CES 2) inhibitors from traditional Chinese medicine, we found that the extract of Alisma orientale significantly inhibited human CES 2 in vitro. The investigation on A. orientale led to the isolation of a new protostane-type triterpenoid alismanin I (1). Its structure was determined according to HRESIMS, 1D and 2D NMR spectra. Alismanin 1(1) displayed significantly inhibitory activity against human CES 2 with IC50 value of 131 0.09 pM assayed by human CES 2-mediated DDAB hydrolysis. According to its inhibition kinetic result, compound I was a noncompetitive type inhibitor, and its Ki was 3.65 pM. Its inhibitory effect was confirmed in living cell level through a visual manner. The potential interaction mechanism of compound 1 with human CES 2 was also analyzed by circular dichroism (CD) spectrum and molecular docking. (C) 2019 Elsevier B.V. All rights reserved.