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-3H-pyrrolo[2,3,4-ij]quinolizine 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.