New dimer and trimer of chalcone derivatives from anti-inflammatory and antinociceptive extracts of Schinopsis brasiliensis roots

Schinopsis brasiliensis Engl. is an endemic tree of the Brazilian semi-arid regions belonging to the Anacardiaceae family. It is the main representative of the genus Schinopsis, mostly native to Brazil and popularly known as "braúna" or "baraúna". Different parts of this plant are employed in Brazilian folk medicines to treat inflammation in general, sexual impotence, cough, and influenza. This work describes the antinociceptive (acetic acid-induced writhing and formalin-induced nociception) and anti-inflammatory (paw edema and neutrophil migration) activities of the extract of the root of S. brasiliensis. Besides, the evaluation of total phenolic compounds and antioxidant, antimicrobial (including MRSA bacteria), and acetylcholinesterase inhibition activities were also determined. The pure compounds were isolated by different chromatographic techniques and their chemical structures have been unambiguously elucidated based on extensive spectroscopic methods, including 1D (1H, 13C, DEPT, and NOEdiff) and 2D (HSQC, HMBC, and NOESY) NMR experiments, MS data, and comparison with the literature data of similar compounds. The antinociceptive and anti-inflammatory activities were evaluated by acid acetic writhing test, formalin paw edema, and by the investigation of neutrophil migration to the peritoneal cavities of mice. For antimicrobial evaluation were determined MIC and MBC, antioxidant activities were obtained by TPC and DPPH tests, and AChE inhibition by Elmann's methodology. The extracts showed antinociceptive and anti-inflammatory activities and two unusual new compounds, a cyclobutanyl chalcone trimer (schinopsone A) and a cyclohexene-containing chalcone dimer (schinopsone B), with six known compounds were isolated from the active extracts. Additionally, the acetylcholinesterase inhibitory activity for isolated compounds was reported for the first time in this study. Molecular docking studies indicated that the isolated compounds are responsible for the interaction with anti-inflammatory targets (COX 1 and 2 and LOX) with variable binding affinities, indicating a possible mechanism of action of these compounds. These findings indicate for the first time the correlation between the anti-inflammatory activity different enriched polyphenol-organic soluble fractions of S. brasiliensis, and it contributes to the understanding of the anti-inflammatory potential of S. brasiliensis. [Display omitted] •Chalcone Dimer and trimers were isolated from Schinopsis bras