Synthesis, Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring β-Amyrenone

摘要

Urease enzyme (UE) has been reported to be a potent virulence factor for Helicobacter pylori (HP) bacteria indicated to be responsible for various gastrointestinal diseases. Therefore, the spread of HP, currently regarded by the World Health Organization as a class 1 carcinogen, could be better controlled by targeting UE. It is in this line that we have synthesized three new derivatives ( 2 – 4 ) of the naturally occurring olean-12-en-3-one ( 1 ), which was previously isolated from the figs of Ficus vallis - choudae Delile (Moraceae). Among the synthesized compounds, 3 and 4 contain an indole moiety. Their structures were unambiguously assigned by spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The starting material and the synthesized compounds were screened for UE inhibition activity, and showed significant activities with IC _(50) values ranging from 14.5 to 24.6?μM, with compound ( 1 ) being the most potent as compared to the positive control thiourea (IC _(50) ?=?21.6?μM). Amongst the synthetic derivatives, compound 4 was the most potent (IC _(50) ?=?17.9?μM), while the others showed activities close to that of the control. In addition, molecular docking study of target compounds 2 – 4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors. Graphical Abstract Electronic supplementary material The online version of this article (10.1007/s13659-018-0193-7) contains supplementary material, which is available to authorized users.