Sophflarines F–K: matrine-based alkaloids with a rare aromatic system from Sophora flavescens and their anti-inflammatory and synergistic antibacterial effects

Abstract Six new matrine-based alkaloids, sophflarines F–K (1–6) , featuring a rare aromatic system, were obtained from the water-soluble alkaloid fractions of Sophora flavescens by UV-guided separation. Their structures were elucidated by the interpretation of spectroscopic analyses, quantum chemical calculation, and X-ray diffraction data. Compounds 1 and 2 represent highly modified 15,16- seco -17- nor -matrine derivatives incorporating a rare 4,5-dihydro-3 H -pyrrolo2,3,4-ijquinolizine moiety, while compound 5 possesses an unusual 6/6/6–5 tetracyclic skeleton. A copper sulfate-induced zebrafish assay revealed that compounds 1 , 4 , and 5 exhibited moderate anti-inflammatory activity at non-toxic concentrations. Checkerboard assays demonstrated that compounds 5 and 6 potentiated colistin activity against Escherichia coli ATCC25922 and BW25113- mcr -1, reducing colistin MIC values by 16- and 32-fold, respectively. These findings expand the structural diversity of aromatic matrine-type alkaloids and highlight their potential as anti-inflammatory agents and antibacterial adjuvants. Graphical Abstract