In vitrobiological evaluation and in silicostudies of linear diarylheptanoids from Curcuma aromaticaSalisb. as urease inhibitorsElectronic supplementary information (ESI) available: 1D, 2D-NMR, HRMSESI, FT-IR spectra of three new compounds (1–2) together with 1D-NMR spectra of six known compounds (4–9); design and validation of the docking model; binding poses and interactions the considered compounds in the active site of urease. See DOI: https://doi.org/10.1039/d3md00645j

Plants of the Zingiberaceaefamily, specifically those belonging to the Curcumaspecies, are commonly under consideration as potential therapeutic agents for the management of gastrointestinal diseases. In this study, we carried out a phytochemical study on Curcuma aromaticaSalisb. (or so-called “Nghe trang” in Vietnamese) grown in Vietnam, which yields three newly discovered 3,5-diacetoxy diarylheptanoids (1–3) and six known 3,5-dihydroxyl diarylheptanoids (4–9). The bioactivity assessment shows that all isolated compounds, except compounds 3, 7, and 8, could inhibit urease. Compounds 4and 9significantly inhibit urease, with an IC50value of 9.6 and 21.4 μM, respectively, more substantial than the positive control, hydroxyurea (IC50= 77.4 μM). The structure–activity relationship (SAR) of linear diarylheptanoids was also established, suggesting that the hydroxyl groups at any position of skeleton diarylheptanoids are essential for exerting anti-urease action. Through a comparative analysis of the binding sites of hydroxyurea and diarylheptanoid compounds viaour constructed in silicomodel, the mechanism of action of diarylheptanoid compounds is predicted to bind to the dynamic region close to the dinickel active center, resulting in a loss of catalytic activity. Such insights certainly help design and/or find diarylheptanoid-based compounds for treating gastric ulcers through inhibiting urease.